Insulin - wikipedia Insulin This article is about the insulin protein. For uses of insulin in treating diabetes, see insulin ( medication ). Not to be confused with Inulin. INS Available structures PDB Ortholog search : PDBe RCSB show List of PDB id codes 1A7F, 1AI0, 1AIY, 1B9E, 1BEN, 1EFE, 1EV3, 1EV6, 1EVR, 1FU2, 1FUB, 1G7A, 1G7B, 1GUJ, 1HIQ, 1HIS, 1HIT, 1HLS, 1HTV, 1HUI, 1IOG, 1IOH, 1J73, 1JCA, 1JCO, 1K3M, 1KMF, 1LKQ, 1LPH, 1MHI, 1MHJ, 1MSO, 1OS3, 1OS4, 1Q4V, 1QIY, 1QIZ, 1QJ0, 1RWE, 1SF1, 1SJT, 1SJU, 1T0C, 1T1K, 1T1P, 1T1Q, 1TRZ, 1TYL, 1TYM, 1UZ9, 1VKT, 1W8P, 1XDA, 1XGL, 1XW7, 1ZEG, 1ZEH, 1ZNJ, 2AIY, 2C8Q, 2C8R, 2CEU, 2G54, 2G56, 2H67, 2HH4, 2HHO, 2HIU, 2JMN, 2JUM, 2JUU, 2JUV, 2JV1, 2JZQ, 2K91, 2K9R, 2KJJ, 2KJU, 2KQP, 2KQQ, 2KXK, 2L1Y, 2L1Z, 2LGB, 2M1D, 2M1E, 2M2M, 2M2N, 2M2O, 2M2P, 2OLY, 2OLZ, 2OM0, 2OM1, 2OMG, 2OMH, 2OMI, 2QIU, 2R34, 2R35, 2R36, 2RN5, 2VJZ, 2VK0, 2W44, 2WBY, 2WC0, 2WRU, 2WRV, 2WRW, 2WRX, 2WS0, 2WS1, 2WS4, 2WS6, 2WS7, 3AIY, 3BXQ, 3E7Y, 3E7Z, 3EXX, 3FQ9, 3HYD, 3I3Z, 3I40, 3ILG, 3INC, 3IR0, 3Q6E, 3ROV, 3TT8, 3U4N, 3UTQ, 3UTS, 3UTT, 3V19, 3V1G, 3W11, 3W12, 3W13, 3W7Y, 3W7Z, 3W80, 3ZI3, 3ZQR, 3ZS2, 3ZU1, 4AIY, 4AJX, 4AJZ, 4AK0, 4AKJ, 4EFX, 4EWW, 4EWX, 4EWZ, 4EX0, 4EX1, 4EXX, 4EY1, 4EY9, 4EYD, 4EYN, 4EYP, 4F0N, 4F0O, 4F1A, 4F1B, 4F1C, 4F1D, 4F1F, 4F1G, 4F4T, 4F4V, 4F51, 4F8F, 4FG3, 4FKA, 4GBC, 4GBI, 4GBK, 4GBL, 4GBN, 4IUZ, 5AIY, 2LWZ, 3JSD, 3KQ6, 3P2X, 3P33, 1JK8, 2MLI, 2MPG, 2MPI, 2MVC, 2MVD, 2OMQ, 4CXL, 4CXN, 4CY7, 4IYD, 4IYF, 4NIB, 4OGA, 4P65, 4Q5Z, 4RXW, 4UNE, 4UNG, 4UNH, 4XC4, 4WDI, 4Z76, 4Z77, 4Z78, 2N2W, 5CO6, 5ENA, 4Y19, 5BQQ, 5BOQ, 2N2V, 5CNY, 5CO9, 5EN9, 4Y1A, 2N2X, 5BPO, 5CO2, 5BTS, 5HYJ, 5C0D Identifiers Aliases INS, IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10, insulin External IDs MGI : 96573 HomoloGene : 173 GeneCards : INS hide Gene location ( Human ) Chr. Chromosome 11 ( human ) Band 11p15. 5 Start 2,159,779 bp End 2,161,341 bp show Gene location ( Mouse ) Chr. Chromosome 7 ( mouse ) Band 7 F5 7 88.0 cM Start 142,678,656 bp End 142,743,381 bp hide RNA expression pattern More reference expression data show Gene ontology Molecular function insulin receptor binding identical protein binding protease binding insulin - like growth factor receptor binding protein binding hormone activity Cellular component endoplasmic reticulum lumen transport vesicle Golgi membrane secretory granule lumen Golgi lumen endoplasmic reticulum - Golgi intermediate compartment membrane endosome lumen extracellular region extracellular space Biological process negative regulation of NAD ( P ) H oxidase activity positive regulation of DNA replication positive regulation of MAPK cascade positive regulation of brown fat cell differentiation positive regulation of cell differentiation MAPK cascade positive regulation of respiratory burst positive regulation of cytokine secretion positive regulation of phosphatidylinositol 3 - kinase signaling negative regulation of protein oligomerization positive regulation of NF - kappaB transcription factor activity negative regulation of respiratory burst involved in inflammatory response cell - cell signaling positive regulation of nitric oxide biosynthetic process positive regulation of glycolytic process positive regulation of nitric - oxide synthase activity positive regulation of protein autophosphorylation activation of protein kinase B activity wound healing positive regulation of mitotic nuclear division negative regulation of feeding behavior cellular protein metabolic process positive regulation of peptide hormone secretion negative regulation of protein catabolic process positive regulation of cell migration acute - phase response regulation of protein secretion positive regulation of glycogen biosynthetic process positive regulation of protein kinase B signaling G - protein coupled receptor signaling pathway glucose transport regulation of cellular amino acid metabolic process negative regulation of oxidative stress - induced intrinsic apoptotic signaling pathway ER to Golgi vesicle - mediated transport negative regulation of lipid catabolic process positive regulation of cell growth negative regulation of glycogen catabolic process positive regulation of insulin receptor signaling pathway glucose metabolic process negative regulation of acute inflammatory response negative regulation of protein secretion positive regulation of peptidyl - tyrosine phosphorylation glucose homeostasis positive regulation of cell proliferation fatty acid homeostasis positive regulation of cellular protein metabolic process regulation of transmembrane transporter activity negative regulation of gluconeogenesis negative regulation of fatty acid metabolic process regulation of protein localization regulation of transcription, DNA - templated positive regulation of lipid biosynthetic process carbohydrate metabolic process negative regulation of proteolysis alpha - beta T cell activation positive regulation of protein localization to nucleus positive regulation of glucose import insulin receptor signaling pathway positive regulation of gene expression positive regulation of blood vessel diameter negative regulation of blood vessel diameter regulation of receptor activity response to L - arginine Sources : Amigo / QuickGO Orthologs Species Human Mouse Entrez 3630 16334 Ensembl ENSG00000254647 ENSMUSG00000000215 UniProt P01308 P01326 RefSeq ( mRNA ) NM_000207 NM_001185097 NM_001185098 NM_001291897 NM_001185083 NM_001185084 NM_008387 RefSeq ( protein ) show NP_000198 NP_001172026 NP_001172027 NP_001278826 NP_000198. 1 NP_001172026. 1 NP_001172027. 1 NP_001278826. 1 NP_001172012 NP_001172013 NP_032413 Location ( UCSC ) Chr 11 : 2.16 -- 2.16 Mb Chr 7 : 142.68 -- 142.74 Mb PubMed search Wikidata View / Edit Human View / Edit Mouse Insulin ( from Latin insula, island ) is a peptide hormone produced by beta cells of the pancreatic islets ; it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of carbohydrates, especially glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats ( triglycerides ) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations, also known as blood sugar levels. When the glucose level is high, the beta cells secrete insulin into the blood ; when glucose levels are low, secretion of insulin is inhibited. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner : increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. If beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting. In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta - cells, reduced secretory function of islet beta - cells that survive, and peripheral tissue insulin resistance. Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, and unresponsive to the concentration of glucose in the blood. Insulin is still secreted into the blood in response to the blood glucose. As a result, the insulin levels, even when the blood sugar level is normal, are much higher than they are in healthy persons. The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a dimer of an A-chain and a B - chain, which are linked together by disulfide bonds. Insulin 's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness ( in carbohydrate metabolism effects ) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies. The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. Contents 1 Evolution and species distribution 2 Gene 2.1 Alleles 2.2 Regulation 3 Protein structure 4 Synthesis, physiological effects, and degradation 4.1 Synthesis 4.2 Release 4.3 Oscillations 4.4 Blood insulin level 4.5 Signal transduction 4.6 Physiological effects 4.7 Degradation 4.8 Regulator of endocannabinoid metabolism 5 Hypoglycemia 6 Diseases and syndromes 7 Medical uses 8 History of study 8.1 Discovery 8.2 Extraction and purification 8.3 Synthesis 8.4 Nobel Prizes 8.4. 1 Controversy 9 See also 10 References 11 Further reading 12 External links Evolution and species distribution Insulin may have originated more than a billion years ago. The molecular origins of insulin go at least as far back as the simplest unicellular eukaryotes. Apart from animals, insulin - like proteins are also known to exist in the Fungi and Protista kingdoms. Insulin is produced by beta cells of the pancreatic islets in most vertebrates and by the Brockmann body in some teleost fish. Cone snails Conus geographus and Conus tulipa, venomous sea snails that hunt small fish, use modified forms of insulin in their venom cocktails. The insulin toxin, closer in structure to fishes ' than to snails ' native insulin, slows down the prey fishes by lowering their blood glucose levels. Gene The preproinsulin precursor of insulin is encoded by the INS gene. Alleles A variety of mutant alleles with changes in the coding region have been identified. A read - through gene, INS - IGF2, overlaps with this gene at the 5 ' region and with the IGF2 gene at the 3 ' region. Regulation Diagram of insulin regulation upon high blood glucose In the pancreatic β cells, glucose is the primary physiological stimulus for the regulation of insulin synthesis. Insulin is mainly regulated through the transcription factors PDX1, NeuroD1, and MafA. PDX1 ( Pancreatic and duodenal homeobox protein 1 ) is in the nuclear periphery upon low blood glucose levels interacting with corepressors HDAC1 and 2 which is downregulating the insulin secretion. An increase in blood glucose levels causes phosphorylation of PDX1 and it translocates centrally and binds the A3 element within the insulin promoter. Upon translocation it interacts with coactivators HAT p300 and acetyltransferase set 7 / 9. PDX1 affects the histone modifications through acetylation and deacetylation as well as methylation. It is also said to suppress glucagon. NeuroD1, also known as β2, regulates insulin exocytosis in pancreatic β cells by directly inducing the expression of genes involved in exocytosis. It is localized in the cytosol, but in response to high glucose it becomes glycosylated by OGT and / or phosphorylated by ERK, which causes translocation to the nucleus. In the nucleus β2 heterodimerizes with E47, binds to the E1 element of the insulin promoter and recruits co-activator p300 which acetylates β2. It is able to interact with other transcription factors as well in activation of the insulin gene. MafA is degraded by proteasomes upon low blood glucose levels. Increased levels of glucose make an unknown protein glycosylated. This protein works as a transcription factor for MafA in an unknown manner and MafA is transported out of the cell. MafA is then translocated back into the nucleus where it binds the C1 element of the insulin promoter. These transcription factors work synergistically and in a complex arrangement. Increased blood glucose can after a while destroy the binding capacities of these proteins, and therefore reduce the amount of insulin secreted, causing diabetes. The decreased binding activities can be mediated by glucose induced oxidative stress and antioxidants are said to prevent the decreased insulin secretion in glucotoxic pancreatic β cells. Stress signalling molecules and reactive oxygen species inhibits the insulin gene by interfering with the cofactors binding the transcription factors and the transcription factors it self. Several regulatory sequences in the promoter region of the human insulin gene bind to transcription factors. In general, the A-boxes bind to Pdx1 factors, E-boxes bind to NeuroD, C - boxes bind to MafA, and cAMP response elements to CREB. There are also silencers that inhibit transcription. Regulatory sequences and their transcription factors for the insulin gene. Regulatory sequence binding transcription factors ILPR Par1 A5 Pdx1 negative regulatory element ( NRE ) glucocorticoid receptor, Oct1 Z ( overlapping NRE and C2 ) ISF C2 Pax4, MafA ( ? ) E2 USF1 / USF2 A3 Pdx1 CREB RE -- CREB RE CREB, CREM A2 -- CAAT enhancer binding ( CEB ) ( partly overlapping A2 and C1 ) -- C1 -- E1 E2A, NeuroD1, HEB A1 Pdx1 G1 -- Protein structure See also : Insulin / IGF / Relaxin family and Insulin and its analog structure Within vertebrates, the amino acid sequence of insulin is strongly conserved. Bovine insulin differs from human in only three amino acid residues, and porcine insulin in one. Even insulin from some species of fish is similar enough to human to be clinically effective in humans. Insulin in some invertebrates is quite similar in sequence to human insulin, and has similar physiological effects. The strong homology seen in the insulin sequence of diverse species suggests that it has been conserved across much of animal evolutionary history. The C - peptide of proinsulin ( discussed later ), however, differs much more among species ; it is also a hormone, but a secondary one. SS - linked insulin monomer The primary structure of bovine insulin was first determined by Frederick Sanger in 1951. After that, this polypeptide was synthesized independently by several groups. The 3 - dimensional structure of insulin was determined by X-ray crystallography in Dorothy Hodgkin 's laboratory in 1969 ( PDB file 1ins ). Insulin is produced and stored in the body as a hexamer ( a unit of six insulin molecules ), while the active form is the monomer. The hexamer is an inactive form with long - term stability, which serves as a way to keep the highly reactive insulin protected, yet readily available. The hexamer - monomer conversion is one of the central aspects of insulin formulations for injection. The hexamer is far more stable than the monomer, which is desirable for practical reasons ; however, the monomer is a much faster - reacting drug because diffusion rate is inversely related to particle size. A fast - reacting drug means insulin injections do not have to precede mealtimes by hours, which in turn gives people with diabetes more flexibility in their daily schedules. Insulin can aggregate and form fibrillar interdigitated beta - sheets. This can cause injection amyloidosis, and prevents the storage of insulin for long periods. Synthesis, physiological effects, and degradation Synthesis Insulin is produced in the pancreas and the Brockmann body ( in some fish ), and released when any of several stimuli are detected. These stimuli include ingested protein and glucose in the blood produced from digested food. Carbohydrates can be polymers of simple sugars or the simple sugars themselves. If the carbohydrates include glucose, then that glucose will be absorbed into the bloodstream and blood glucose level will begin to rise. In target cells, insulin initiates a signal transduction, which has the effect of increasing glucose uptake and storage. Finally, insulin is degraded, terminating the response. Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent ; prepared insulin is stored awaiting secretion. Both C - peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale. In mammals, insulin is synthesized in the pancreas within the beta cells. One million to three million pancreatic islets form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine portion accounts for only 2 % of the total mass of the pancreas. Within the pancreatic islets, beta cells constitute 65 -- 80 % of all the cells. Insulin consists of two polypeptide chains, the A - and B - chains, linked together by disulfide bonds. It is however first synthesized as a single polypeptide called preproinsulin in beta cells. Preproinsulin contains a 24 - residue signal peptide which directs the nascent polypeptide chain to the rough endoplasmic reticulum ( RER ). The signal peptide is cleaved as the polypeptide is translocated into lumen of the RER, forming proinsulin. In the RER the proinsulin folds into the correct conformation and 3 disulfide bonds are formed. About 5 -- 10 min after its assembly in the endoplasmic reticulum, proinsulin is transported to the trans - Golgi network ( TGN ) where immature granules are formed. Transport to the TGN may take about 30 min. Proinsulin undergoes maturation into active insulin through the action of cellular endopeptidases known as prohormone convertases ( PC1 and PC2 ), as well as the exoprotease carboxypeptidase E. The endopeptidases cleave at 2 positions, releasing a fragment called the C - peptide, and leaving 2 peptide chains, the B - and A - chains, linked by 2 disulfide bonds. The cleavage sites are each located after a pair of basic residues ( lysine - 64 and arginine - 65, and arginine - 31 and − 32 ). After cleavage of the C - peptide, these 2 pairs of basic residues are removed by the carboxypeptidase. The C - peptide is the central portion of proinsulin, and the primary sequence of proinsulin goes in the order `` B-C-A '' ( the B and A chains were identified on the basis of mass and the C - peptide was discovered later ). The resulting mature insulin is packaged inside mature granules waiting for metabolic signals ( such as leucine, arginine, glucose and mannose ) and vagal nerve stimulation to be exocytosed from the cell into the circulation. The endogenous production of insulin is regulated in several steps along the synthesis pathway : At transcription from the insulin gene In mRNA stability At the mRNA translation In the posttranslational modifications Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to Alzheimer 's disease. Insulin release is stimulated also by beta - 2 receptor stimulation and inhibited by alpha - 1 receptor stimulation. In addition, cortisol, glucagon and growth hormone antagonize the actions of insulin during times of stress. Insulin also inhibits fatty acid release by hormone sensitive lipase in adipose tissue. Release See also : Blood glucose regulation Beta cells in the islets of Langerhans release insulin in two phases. The first - phase release is rapidly triggered in response to increased blood glucose levels, and lasts about 10 minutes. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar, peaking in 2 to 3 hours. Reduced first - phase insulin release may be the earliest detectable beta cell defect predicting onset of type 2 diabetes. First - phase release and insulin sensitivity are independent predictors of diabetes. The description of first phase release is as follows : Glucose enters the β - cells through the glucose transporters, GLUT2. These glucose transporters have a relatively low affinity for glucose, ensuring that the rate of glucose entry into the β - cells is proportional to the extracellular glucose concentration ( within the physiological range ). At low blood sugar levels very little glucose enters the β - cells ; at high blood glucose concentrations large quantities of glucose enter these cells. The glucose that enters the β - cell is phosphorylated to glucose - 6 - phosphate ( G - 6 - P ) by glucokinase ( hexokinase IV ) which is not inhibited by G - 6 - P in the way that the hexokinases in other tissues ( hexokinase I -- III ) are affected by this product. This means that the intracellular G - 6 - P concentration remains proportional to the blood sugar concentration. Glucose - 6 - phosphate enters glycolytic pathway and then, via the pyruvate dehydrogenase reaction, into the Krebs cycle, where multiple, high - energy ATP molecules are produced by the oxidation of acetyl CoA ( the Krebs cycle substrate ), leading to a rise in the ATP : ADP ratio within the cell. An increased intracellular ATP : ADP ratio closes the ATP - sensitive SUR1 / Kir6. 2 potassium channel ( see sulfonylurea receptor ). This prevents potassium ions ( K ) from leaving the cell by facilitated diffusion, leading to a buildup of intracellular potassium ions. As a result, the inside of the cell becomes less negative with respect to the outside, leading to the depolarization of the cell surface membrane. Upon depolarization, voltage - gated calcium ion ( Ca ) channels open, allowing calcium ions to move into the cell by facilitated diffusion. The cytosolic calcium ion concentration can also be increased by calcium release from intracellular stores via activation of ryanodine receptors. The calcium ion concentration in the cytosol of the beta cells can also, or additionally, be increased through the activation of phospholipase C resulting from the binding of an extracellular ligand ( hormone or neurotransmitter ) to a G protein - coupled membrane receptor. Phospholipase C cleaves the membrane phospholipid, phosphatidyl inositol 4, 5 - bisphosphate, into inositol 1, 4, 5 - trisphosphate and diacylglycerol. Inositol 1, 4, 5 - trisphosphate ( IP3 ) then binds to receptor proteins in the plasma membrane of the endoplasmic reticulum ( ER ). This allows the release of Ca ions from the ER via IP3 - gated channels, which raises the cytosolic concentration of calcium ions independently of the effects of a high blood glucose concentration. Parasympathetic stimulation of the pancreatic islets operates via this pathway to increase insulin secretion into the blood. The significantly increased amount of calcium ions in the cells ' cytoplasm causes the release into the blood of previously synthesized insulin, which has been stored in intracellular secretory vesicles. This is the primary mechanism for release of insulin. Other substances known to stimulate insulin release include the amino acids arginine and leucine, parasympathetic release of acetylcholine ( acting via the phospholipase C pathway ), sulfonylurea, cholecystokinin ( CCK, also via phospholipase C ), and the gastrointestinally derived incretins, such as glucagon - like peptide - 1 ( GLP - 1 ) and glucose - dependent insulinotropic peptide ( GIP ). Release of insulin is strongly inhibited by norepinephrine ( noradrenaline ), which leads to increased blood glucose levels during stress. It appears that release of catecholamines by the sympathetic nervous system has conflicting influences on insulin release by beta cells, because insulin release is inhibited by α - adrenergic receptors and stimulated by β - adrenergic receptors. The net effect of norepinephrine from sympathetic nerves and epinephrine from adrenal glands on insulin release is inhibition due to dominance of the α - adrenergic receptors. When the glucose level comes down to the usual physiologic value, insulin release from the β - cells slows or stops. If the blood glucose level drops lower than this, especially to dangerously low levels, release of hyperglycemic hormones ( most prominently glucagon from islet of Langerhans alpha cells ) forces release of glucose into the blood from the liver glycogen stores, supplemented by gluconeogenesis if the glycogen stores become depleted. By increasing blood glucose, the hyperglycemic hormones prevent or correct life - threatening hypoglycemia. Evidence of impaired first - phase insulin release can be seen in the glucose tolerance test, demonstrated by a substantially elevated blood glucose level at 30 minutes after the ingestion of a glucose load ( 75 or 100 g of glucose ), followed by a slow drop over the next 100 minutes, to remain above 120 mg / 100 ml after two hours after the start of the test. In a normal person the blood glucose level is corrected ( and may even be slightly over-corrected ) by the end of the test. Oscillations Main article : Insulin oscillations Insulin release from pancreas oscillates with a period of 3 -- 6 minutes. Even during digestion, in general, one or two hours following a meal, insulin release from the pancreas is not continuous, but oscillates with a period of 3 -- 6 minutes, changing from generating a blood insulin concentration more than about 800 p mol / l to less than 100 pmol / l. This is thought to avoid downregulation of insulin receptors in target cells, and to assist the liver in extracting insulin from the blood. This oscillation is important to consider when administering insulin - stimulating medication, since it is the oscillating blood concentration of insulin release, which should, ideally, be achieved, not a constant high concentration. This may be achieved by delivering insulin rhythmically to the portal vein or by islet cell transplantation to the liver. Blood insulin level Further information : Insulin index The idealized diagram shows the fluctuation of blood sugar ( red ) and the sugar - lowering hormone insulin ( blue ) in humans during the course of a day containing three meals. In addition, the effect of a sugar - rich versus a starch - rich meal is highlighted. The blood insulin level can be measured in international units, such as μIU / mL or in molar concentration, such as pmol / L, where 1 μIU / mL equals 6.945 pmol / L. A typical blood level between meals is 8 -- 11 μIU / mL ( 57 -- 79 pmol / L ). Signal transduction The effects of insulin are initiated by its binding to a receptor present in the cell membrane. The receptor molecule contains an α - and β subunits. Two molecules are joined to form what is known as a homodimer. Insulin binds to the α - subunits of the homodimer, which faces the extracellular side of the cells. The β subunits have tyrosine kinase enzyme activity which is triggered by the insulin binding. This activity provokes the autophosphorylation of the β subunits and subsequently the phosphorylation of proteins inside the cell known as insulin receptor substrates ( IRS ). The phosphorylation of the IRS activates a signal transduction cascade that leads to the activation of other kinases as well as transcription factors that mediate the intracellular effects of insulin. The cascade that leads to the insertion of GLUT4 glucose transporters into the cell membranes of muscle and fat cells, and to the synthesis of glycogen in liver and muscle tissue, as well as the conversion of glucose into triglycerides in liver, adipose, and lactating mammary gland tissue, operates via the activation, by IRS - 1, of phosphoinositol 3 kinase ( PI3K ). This enzyme converts a phospholipid in the cell membrane by the name of phosphatidylinositol 4, 5 - bisphosphate ( PIP2 ), into phosphatidylinositol 3, 4, 5 - triphosphate ( PIP3 ), which, in turn, activates protein kinase B ( PKB ). Activated PKB facilitates the fusion of GLUT4 containing endosomes with the cell membrane, resulting in an increase in GLUT4 transporters in the plasma membrane. PKB also phosphorylates glycogen synthase kinase ( GSK ), thereby inactivating this enzyme. This means that its substrate, glycogen synthase ( GS ), can not be phosphorylated, and remains dephosphorylated, and therefore active. The active enzyme, glycogen synthase ( GS ), catalyzes the rate limiting step in the synthesis of glycogen from glucose. Similar dephosphorylations affect the enzymes controlling the rate of glycolysis leading to the synthesis of fats via malonyl - CoA in the tissues that can generate triglycerides, and also the enzymes that control the rate of gluconeogenesis in the liver. The overall effect of these final enzyme dephosphorylations is that, in the tissues that can carry out these reactions, glycogen and fat synthesis from glucose are stimulated, and glucose production by the liver through glycogenolysis and gluconeogenesis are inhibited. The breakdown of triglycerides by adipose tissue into free fatty acids and glycerol is also inhibited. After the intracellular signal that resulted from the binding of insulin to its receptor has been produced, termination of signaling is then needed. As mentioned below in the section on degradation, endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling. In addition, the signaling pathway is also terminated by dephosphorylation of the tyrosine residues in the various signaling pathways by tyrosine phosphatases. Serine / Threonine kinases are also known to reduce the activity of insulin. The structure of the insulin -- insulin receptor complex has been determined using the techniques of X-ray crystallography. Physiological effects Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor ( 1 ), which starts many protein activation cascades ( 2 ). These include translocation of Glut - 4 transporter to the plasma membrane and influx of glucose ( 3 ), glycogen synthesis ( 4 ), glycolysis ( 5 ) and triglyceride synthesis ( 6 ). The insulin signal transduction pathway begins when insulin binds to the insulin receptor proteins. Once the transduction pathway is completed, the GLUT - 4 storage vesicles becomes one with the cellular membrane. As a result, the GLUT - 4 protein channels become embedded into the membrane, allowing glucose to be transported into the cell. The actions of insulin on the global human metabolism level include : Increase of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue ( about two - thirds of body cells ) Increase of DNA replication and protein synthesis via control of amino acid uptake Modification of the activity of numerous enzymes. The actions of insulin ( indirect and direct ) on cells include : Stimulates the uptake of glucose -- Insulin decreases blood glucose concentration by inducing intake of glucose by the cells. This is possible because Insulin causes the insertion of the GLUT4 transporter in the cell membranes of muscle and fat tissues which allows glucose to enter the cell. Increased fat synthesis -- insulin forces fat cells to take in blood glucose, which is converted into triglycerides ; decrease of insulin causes the reverse. Increased esterification of fatty acids -- forces adipose tissue to make neutral fats ( i.e., triglycerides ) from fatty acids ; decrease of insulin causes the reverse. Decreased lipolysis -- forces reduction in conversion of fat cell lipid stores into blood fatty acids and glycerol ; decrease of insulin causes the reverse. Induce glycogen synthesis -- When glucose levels are high, insulin induces the formation of glycogen by the activation of the hexokinase enzyme, which adds a phosphate group in glucose, thus resulting in a molecule that can not exit the cell. At the same time, insulin inhibits the enzyme glucose - 6 - phosphatase, which removes the phosphate group. These two enzymes are key for the formation of glycogen. Also, insulin activates the enzymes phosphofructokinase and glycogen synthase which are responsible for glycogen synthesis. Decreased gluconeogenesis and glycogenolysis -- decreases production of glucose from noncarbohydrate substrates, primarily in the liver ( the vast majority of endogenous insulin arriving at the liver never leaves the liver ) ; increase of insulin causes glucose production by the liver from assorted substrates. Decreased proteolysis -- decreasing the breakdown of protein Decreased autophagy -- decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely. Increased amino acid uptake -- forces cells to absorb circulating amino acids ; decrease of insulin inhibits absorption. Arterial muscle tone -- forces arterial wall muscle to relax, increasing blood flow, especially in microarteries ; decrease of insulin reduces flow by allowing these muscles to contract. Increase in the secretion of hydrochloric acid by parietal cells in the stomach. Increased potassium uptake -- forces cells synthesizing glycogen ( a very spongy, `` wet '' substance, that increases the content of intracellular water, and its accompanying K ions ) to absorb potassium from the extracellular fluids ; lack of insulin inhibits absorption. Insulin 's increase in cellular potassium uptake lowers potassium levels in blood plasma. This possibly occurs via insulin - induced translocation of the Na+ / K+ - ATPase to the surface of skeletal muscle cells. Decreased renal sodium excretion. Insulin also influences other body functions, such as vascular compliance and cognition. Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the co-ordination of a wide variety of homeostatic or regulatory processes in the human body. Insulin also has stimulatory effects on gonadotropin - releasing hormone from the hypothalamus, thus favoring fertility. Degradation Once an insulin molecule has docked onto the receptor and effected its action, it may be released back into the extracellular environment, or it may be degraded by the cell. The two primary sites for insulin clearance are the liver and the kidney. The liver clears most insulin during first - pass transit, whereas the kidney clears most of the insulin in systemic circulation. Degradation normally involves endocytosis of the insulin - receptor complex, followed by the action of insulin - degrading enzyme. An insulin molecule produced endogenously by the beta cells is estimated to be degraded within about one hour after its initial release into circulation ( insulin half - life ~ 4 -- 6 minutes ). Regulator of endocannabinoid metabolism Insulin is a major regulator of endocannabinoid ( EC ) metabolism and insulin treatment has been shown to reduce intracellular ECs, the 2 - arachidonylglycerol ( 2 - AG ) and anandamide ( AEA ), which correspond with insulin - sensitive expression changes in enzymes of EC metabolism. In insulin - resistant adipocytes, patterns of insulin - induced enzyme expression is disturbed in a manner consistent with elevated EC synthesis and reduced EC degradation. Findings suggest that insulin - resistant adipocytes fail to regulate EC metabolism and decrease intracellular EC levels in response to insulin stimulation, whereby obese insulin - resistant individuals exhibit increased concentrations of ECs. This dysregulation contributes to excessive visceral fat accumulation and reduced adiponectin release from abdominal adipose tissue, and further to the onset of several cardiometabolic risk factors that are associated with obesity and type 2 diabetes. Hypoglycemia Main article : Hypoglycemia Hypoglycemia, also known as `` low blood sugar '', is when blood sugar decreases to below normal levels. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly. The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas. Risk is greater in diabetics who have eaten less than usual, exercised more than usual or have drunk alcohol. Other causes of hypoglycemia include kidney failure, certain tumors, such as insulinoma, liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours. Diseases and syndromes This section does not cite any sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. ( July 2018 ) There are several conditions in which insulin disturbance is pathologic : Diabetes mellitus -- general term referring to all states characterized by hyperglycemia Type 1 -- autoimmune - mediated destruction of insulin - producing β - cells in the pancreas, resulting in absolute insulin deficiency Type 2 -- either inadequate insulin production by the β - cells or insulin resistance or both because of reasons not completely understood. there is correlation with diet, with sedentary lifestyle, with obesity, with age and with metabolic syndrome. Causality has been demonstrated in multiple model organisms including mice and monkeys ; Importantly, non-obese people do get Type 2 diabetes due to diet, sedentary lifestyle and unknown risk factors. it is likely that there is genetic susceptibility to develop Type 2 diabetes under certain environmental conditions Other types of impaired glucose tolerance ( see the Diabetes ) Insulinoma -- a tumor of beta cells producing excess insulin or reactive hypoglycemia. Metabolic syndrome -- a poorly understood condition first called Syndrome X by Gerald Reaven. It is currently not clear whether the syndrome has a single, treatable cause, or is the result of body changes leading to type 2 diabetes. It is characterized by elevated blood pressure, dyslipidemia ( disturbances in blood cholesterol forms and other blood lipids ), and increased waist circumference ( at least in populations in much of the developed world ). The basic underlying cause may be the insulin resistance that precedes type 2 diabetes, which is a diminished capacity for insulin response in some tissues ( e.g., muscle, fat ). It is common for morbidities such as essential hypertension, obesity, type 2 diabetes, and cardiovascular disease ( CVD ) to develop. Polycystic ovary syndrome -- a complex syndrome in women in the reproductive years where anovulation and androgen excess are commonly displayed as hirsutism. In many cases of PCOS, insulin resistance is present. Medical uses Main article : Insulin ( medication ) A vial of insulin. It has been given a trade name, Actrapid, by the manufacturer. Biosynthetic human insulin ( insulin human rDNA, INN ) for clinical use is manufactured by recombinant DNA technology. Biosynthetic human insulin has increased purity when compared with extractive animal insulin, enhanced purity reducing antibody formation. Researchers have succeeded in introducing the gene for human insulin into plants as another method of producing insulin ( `` biopharming '' ) in safflower. This technique is anticipated to reduce production costs. Several analogs of human insulin are available. These insulin analogs are closely related to the human insulin structure, and were developed for specific aspects of glycemic control in terms of fast action ( prandial insulins ) and long action ( basal insulins ). The first biosynthetic insulin analog was developed for clinical use at mealtime ( prandial insulin ), Humalog ( insulin lispro ), it is more rapidly absorbed after subcutaneous injection than regular insulin, with an effect 15 minutes after injection. Other rapid - acting analogues are NovoRapid and Apidra, with similar profiles. All are rapidly absorbed due to amino acid sequences that will reduce formation of dimers and hexamers ( monomeric insulins are more rapidly absorbed ). Fast acting insulins do not require the injection - to - meal interval previously recommended for human insulin and animal insulins. The other type is long acting insulin ; the first of these was Lantus ( insulin glargine ). These have a steady effect for an extended period from 18 to 24 hours. Likewise, another protracted insulin analogue ( Levemir ) is based on a fatty acid acylation approach. A myristic acid molecule is attached to this analogue, which associates the insulin molecule to the abundant serum albumin, which in turn extends the effect and reduces the risk of hypoglycemia. Both protracted analogues need to be taken only once daily, and are used for type 1 diabetics as the basal insulin. A combination of a rapid acting and a protracted insulin is also available, making it more likely for patients to achieve an insulin profile that mimics that of the body  ́ s own insulin release. Insulin is usually taken as subcutaneous injections by single - use syringes with needles, via an insulin pump, or by repeated - use insulin pens with disposable needles. Inhaled insulin is also available in the U.S. market now. Synthetic insulin can trigger adverse effects, so some people with diabetes rely on animal - source insulin. Unlike many medicines, insulin currently can not be taken orally because, like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments, whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered orally or sublingually. History of Study Discovery In 1869, while studying the structure of the pancreas under a microscope, Paul Langerhans, a medical student in Berlin, identified some previously unnoticed tissue clumps scattered throughout the bulk of the pancreas. The function of the `` little heaps of cells '', later known as the islets of Langerhans, initially remained unknown, but Édouard Laguesse later suggested they might produce secretions that play a regulatory role in digestion. Paul Langerhans ' son, Archibald, also helped to understand this regulatory role. The term `` insulin '' originates from insula, the Latin word for islet / island. In 1889, the physician Oskar Minkowski, in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine, they found sugar, establishing for the first time a relationship between the pancreas and diabetes. In 1901, another major step was taken by the American physician and scientist Eugene Lindsay Opie, when he isolated the role of the pancreas to the islets of Langerhans : `` Diabetes mellitus when the result of a lesion of the pancreas is caused by destruction of the islands of Langerhans and occurs only when these bodies are in part or wholly destroyed ''. The structure of insulin. The left side is a space - filling model of the insulin monomer, believed to be biologically active. Carbon is green, hydrogen white, oxygen red, and nitrogen blue. On the right side is a ribbon diagram of the insulin hexamer, believed to be the stored form. A monomer unit is highlighted with the A chain in blue and the B chain in cyan. Yellow denotes disulfide bonds, and magenta spheres are zinc ions. Over the next two decades researchers made several attempts to isolate the islets ' secretions. In 1906 George Ludwig Zuelzer achieved partial success in treating dogs with pancreatic extract, but he was unable to continue his work. Between 1911 and 1912, E.L. Scott at the University of Chicago tried aqueous pancreatic extracts and noted `` a slight diminution of glycosuria '', but was unable to convince his director of his work 's value ; it was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1915, but World War I interrupted his work and he did not return to it. In 1916, Nicolae Paulescu developed an aqueous pancreatic extract which, when injected into a diabetic dog, had a normalizing effect on blood - sugar levels. He had to interrupt his experiments because of World War I, and in 1921 he wrote four papers about his work carried out in Bucharest and his tests on a diabetic dog. Later that year, he published `` Research on the Role of the Pancreas in Food Assimilation ''. Extraction and purification In October 1920, Canadian Frederick Banting concluded that the digestive secretions that Minkowski had originally studied were breaking down the islet secretion, thereby making it impossible to extract successfully. A surgeon by training, Banting knew certain arteries could be tied off that would lead most of the pancreas to atrophy, while leaving the islets of Langerhans intact. He reasoned that a relatively pure extract could be made from the islets once most of the rest of the pancreas was gone. He jotted a note to himself : `` Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosuria. '' In the spring of 1921, Banting traveled to Toronto to explain his idea to J.J.R. Macleod, Professor of Physiology at the University of Toronto. Macleod was initially skeptical, since Banting had no background in research and was not familiar with the latest literature, but he agreed to provide lab space for Banting to test out his ideas. Macleod also arranged for two undergraduates to be Banting 's lab assistants that summer, but Banting required only one lab assistant. Charles Best and Clark Noble flipped a coin ; Best won the coin toss and took the first shift. This proved unfortunate for Noble, as Banting keep Best for the entire summer and eventually shared half his Nobel Prize money and credit for the discovery with Best. On 30 July 1921, Banting and Best successfully isolated an extract ( `` isleton '' ) from the islets of a duct - tied dog and injected it into a diabetic dog, finding that the extract reduced its blood sugar by 40 % in 1 hour. Banting and Best presented their results to Macleod on his return to Toronto in the fall of 1921, but Macleod pointed out flaws with the experimental design, and suggested the experiments be repeated with more dogs and better equipment. He moved Banting and Best into a better laboratory and began paying Banting a salary from his research grants. Several weeks later, the second round of experiments was also a success, and Macleod helped publish their results privately in Toronto that November. Bottlenecked by the time - consuming task of duct - tying dogs and waiting several weeks to extract insulin, Banting hit upon the idea of extracting insulin from the fetal calf pancreas, which had not yet developed digestive glands. By December, they had also succeeded in extracting insulin from the adult cow pancreas. Macleod discontinued all other research in his laboratory to concentrate on the purification of insulin. He invited biochemist James Collip to help with this task, and the team felt ready for a clinical test within a month. On January 11, 1922, Leonard Thompson, a 14 - year - old diabetic who lay dying at the Toronto General Hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled. Over the next 12 days, Collip worked day and night to improve the ox - pancreas extract. A second dose was injected on January 23, completely eliminating the glycosuria that was typical of diabetes without causing any obvious side - effects. The first American patient was Elizabeth Hughes, the daughter of U.S. Secretary of State Charles Evans Hughes. The first patient treated in the U.S. was future woodcut artist James D. Havens ; Dr. John Ralston Williams imported insulin from Toronto to Rochester, New York, to treat Havens. Banting and Best never worked well with Collip, regarding him as something of an interloper, and Collip left the project soon after. Over the spring of 1922, Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure. The drug firm Eli Lilly and Company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April. In November, Lilly 's head chemist, George B. Walden discovered isoelectric precipitation and was able to produce large quantities of highly refined insulin. Shortly thereafter, insulin was offered for sale to the general public. Synthesis Purified animal - sourced insulin was initially the only type of insulin available to diabetics. The amino acid structure of insulin was characterized in the early 1950s by Frederick Sanger, and the first synthetic insulin was produced simultaneously in the labs of Panayotis Katsoyannis at the University of Pittsburgh and Helmut Zahn at RWTH Aachen University in the early 1960s. Synthetic crystalline bovine insulin was achieved by Chinese researchers in 1965. The first genetically engineered, synthetic `` human '' insulin was produced using E. coli in 1978 by Arthur Riggs and Keiichi Itakura at the Beckman Research Institute of the City of Hope in collaboration with Herbert Boyer at Genentech. Genentech, founded by Swanson, Boyer and Eli Lilly and Company, went on in 1982 to sell the first commercially available biosynthetic human insulin under the brand name Humulin. The vast majority of insulin currently used worldwide is now biosynthetic recombinant `` human '' insulin or its analogues. Recombinant insulin is produced either in yeast ( usually Saccharomyces cerevisiae ) or E. coli. In yeast, insulin may be engineered as a single - chain protein with a KexII endoprotease ( a yeast homolog of PCI / PCII ) site that separates the insulin A chain from a c - terminally truncated insulin B chain. A chemically synthesized c - terminal tail is then grafted onto insulin by reverse proteolysis using the inexpensive protease trypsin ; typically the lysine on the c - terminal tail is protected with a chemical protecting group to prevent proteolysis. The ease of modular synthesis and the relative safety of modifications in that region accounts for common insulin analogs with c - terminal modifications ( e.g. lispro, aspart, glulisine ). The Genentech synthesis and completely chemical synthesis such as that by Bruce Merrifield are not preferred because the efficiency of recombining the two insulin chains is low, primarily due to competition with the precipitation of insulin B chain. Nobel Prizes Frederick Banting joined by Charles Best in office, 1924 The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men : Frederick Banting and J.J.R. Macleod. They were awarded the Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin. Banting, insulted that Best was not mentioned, shared his prize with him, and Macleod immediately shared his with James Collip. The patent for insulin was sold to the University of Toronto for one half - dollar. Two other Nobel Prizes have been awarded for work on insulin. British molecular biologist Frederick Sanger determined the primary structure of insulin in 1955, making it the first protein to be sequenced. Sanger was awarded the 1958 Nobel Prize in Chemistry for this work. Rosalyn Sussman Yalow received the 1977 Nobel Prize in Medicine for the development of the radioimmunoassay for insulin. Several Nobel Prizes also have an indirect connection with insulin. George Minot, co-recipient of the 1934 Nobel Prize for the development of the first effective treatment for pernicious anemia, had diabetes mellitus. Dr. William Castle observed that the 1921 discovery of insulin, arriving in time to keep Minot alive, was therefore also responsible for the discovery of a cure for pernicious anemia. Dorothy Hodgkin was awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography. In 1969, after decades of work, Hodgkin determined the spatial conformation of insulin, the so - called tertiary structure, by means of X-ray diffraction studies. Controversy Nicolae Paulescu The work published by Banting, Best, Collip and Macleod represented the preparation of purified insulin extract suitable for use on human patients. Although Paulescu discovered the principles of the treatment, his saline extract could not be used on humans ; he was not mentioned in the 1923 Nobel Prize. Professor Ian Murray was particularly active in working to correct `` the historical wrong '' against Nicolae Paulescu. Murray was a professor of physiology at the Anderson College of Medicine in Glasgow, Scotland, the head of the department of Metabolic Diseases at a leading Glasgow hospital, vice-president of the British Association of Diabetes, and a founding member of the International Diabetes Federation. Murray wrote : Insufficient recognition has been given to Paulescu, the distinguished Romanian scientist, who at the time when the Toronto team were commencing their research had already succeeded in extracting the antidiabetic hormone of the pancreas and proving its efficacy in reducing the hyperglycaemia in diabetic dogs. In a private communication, Professor Arne Tiselius, former head of the Nobel Institute, expressed his personal opinion that Paulescu was equally worthy of the award in 1923. See also Insulin analog Anatomy and physiolology Pancreas Islets of Langerhans Endocrinology Leptin Forms of diabetes mellitus Diabetes mellitus Diabetes mellitus type 1 Diabetes mellitus type 2 Treatment Diabetic coma Insulin therapy Intensive insulinotherapy Insulin pump Conventional insulinotherapy Other medical / diagnostic uses Insulin tolerance test Triple bolus test Insulin Signal Transduction pathway Insulin signal transduction pathway and regulation of blood glucose Other uses Cone Snail venom References ^ Jump up to : GRCh38 : Ensembl release 89 : ENSG00000254647 - Ensembl, May 2017 ^ Jump up to : GRCm38 : Ensembl release 89 : ENSMUSG00000000215 - Ensembl, May 2017 Jump up ^ `` Human PubMed Reference : ''. Jump up ^ `` Mouse PubMed Reference : ''. ^ Jump up to : Voet D, Voet JG ( 2011 ). Biochemistry ( 4th ed. ). New York : Wiley. ^ Jump up to : Stryer L ( 1995 ). Biochemistry ( Fourth ed. ). New York : W.H. Freeman and Company. pp. 773 -- 74. ISBN 0 7167 2009 4. 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Archived from the original on November 23, 2010. Retrieved November 22, 2010. ^ Jump up to : Stretton AO ( October 2002 ). `` The first sequence. Fred Sanger and insulin ''. Genetics. 162 ( 2 ) : 527 -- 32. PMC 1462286. PMID 12399368. Jump up ^ Costin GE ( January 2004 ). `` What is the advantage of having melanin in parts of the central nervous system ( e.g. substantia nigra ) ? ''. IUBMB Life. Time Inc. 56 ( 1 ) : 47 -- 49. doi : 10.1080 / 15216540310001659029. PMID 14992380. Jump up ^ Wollmer A, Dieken ML, Federwisch M, De Meyts P ( 2002 ). Insulin & related proteins structure to function and pharmacology. Boston : Kluwer Academic Publishers. ISBN 1 - 4020 - 0655 - 1. Jump up ^ 邹承鲁 ( Chenglu Zou ) ( 2015 ). `` 对 人工 合成 结晶 牛 胰岛素 的 回忆 ( Memory on the research of synthesizing bovine insulin ) ''. 生命 科学 ( Chinese Bulletin of Life Science ) ( in Simplified Chinese ). 27 ( 6 ) : 777 -- 79. CS1 maint : Unrecognized language ( link ) Jump up ^ Kjeldsen T ( September 2000 ). `` Yeast secretory expression of insulin precursors ''. Applied Microbiology and Biotechnology. 54 ( 3 ) : 277 -- 86. doi : 10.1007 / s002530000402. PMID 11030562. Jump up ^ `` The Nobel Prize in Physiology or Medicine 1923 ''. The Nobel Foundation. Jump up ^ Castle WB ( 1962 ). `` The Gordon Wilson Lecture. A Century of Curiosity About Pernicious Anemia ''. Transactions of the American Clinical and Climatological Association. 73 : 54 -- 80. PMC 2249021. PMID 21408623. Jump up ^ Banting FG, Best CH, Collip JB, Campbell WR, Fletcher AA ( March 1922 ). `` Pancreatic Extracts in the Treatment of Diabetes Mellitus ''. Canadian Medical Association Journal. 12 ( 3 ) : 141 -- 46. PMC 1524425. PMID 20314060. Jump up ^ Drury MI ( July 1972 ). `` The golden jubile of insulin ''. Journal of the Irish Medical Association. 65 ( 14 ) : 355 -- 63. PMID 4560502. Jump up ^ Murray I ( April 1971 ). `` Paulesco and the isolation of insulin ''. Journal of the History of Medicine and Allied Sciences. 26 ( 2 ) : 150 -- 57. doi : 10.1093 / jhmas / XXVI. 2.150. PMID 4930788. Further reading Laws GM, Reaven A ( 1999 ). Insulin resistance : the metabolic syndrome X. Totowa, NJ : Humana Press. doi : 10.1226 / 0896035883. ISBN 0 - 89603 - 588 - 3. Leahy JL, Cefalu WT ( 2002 - 03 - 22 ). Insulin Therapy ( 1st ed. ). New York : Marcel Dekker. ISBN 0 - 8247 - 0711 - 7. Kumar S, O'Rahilly S ( 2005 - 01 - 14 ). Insulin Resistance : Insulin Action and Its Disturbances in Disease. Chichester, England : Wiley. ISBN 0 - 470 - 85008 - 6. Ehrlich A, Schroeder CL ( 2000 - 06 - 16 ). Medical Terminology for Health Professions ( 4th ed. ). Thomson Delmar Learning. ISBN 0 - 7668 - 1297 - 9. Draznin B, LeRoith D ( September 1994 ). Molecular Biology of Diabetes : Autoimmunity and Genetics ; Insulin Synthesis and Secretion. Totowa, New Jersey : Humana Press. doi : 10.1226 / 0896032868. ISBN 0 - 89603 - 286 - 8. Famous Canadian Physicians : Sir Frederick Banting at Library and Archives Canada McKeage K, Goa KL ( 2001 ). `` Insulin glargine : a review of its therapeutic use as a long - acting agent for the management of type 1 and 2 diabetes mellitus ''. Drugs. 61 ( 11 ) : 1599 -- 624. doi : 10.2165 / 00003495 - 200161110 - 00007. PMID 11577797. External links Wikimedia Commons has media related to Insulin. Insulin : entry from protein databank The History of Insulin CBC Digital Archives -- Banting, Best, Macleod, Collip : Chasing a Cure for Diabetes Discovery and Early Development of Insulin, 1920 -- 1925 Secretion of Insulin and Glucagon Insulin signaling pathway Animations of insulin 's action in the body at AboutKidsHealth.ca Types of Insulin for Diabetes Treatment at ApolloSugar.com PDB gallery 1ai0 : R6 HUMAN INSULIN HEXAMER ( NON-SYMMETRIC ), NMR, 10 STRUCTURES 1aiy : R6 HUMAN INSULIN HEXAMER ( SYMMETRIC ), NMR, 10 STRUCTURES 1aph : CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7 - 11 1b17 : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 5.00 COORDINATES ) 1b18 : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 5.53 COORDINATES ) 1b19 : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 5.80 COORDINATES ) 1b2a : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.00 COORDINATES ) 1b2b : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.16 COORDINATES ) 1b2c : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.26 COORDINATES ) 1b2d : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.35 COORDINATES ) 1b2e : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.50 COORDINATES ) 1b2f : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 6.98 COORDINATES ) 1b2g : PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS ( PH 9.00 COORDINATES ) 1b9e : HUMAN INSULIN MUTANT SERB9GLU 1ben : INSULIN COMPLEXED WITH 4 - HYDROXYBENZAMIDE 1bph : CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7 - 11 1cph : CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7 - 11 1dph : CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7 - 11 1ev3 : Structure of the rhombohedral form of the M - cresol / insulin R6 hexamer 1ev6 : Structure of the monoclinic form of the M - cresol / insulin R6 hexamer 1evr : The structure of the resorcinol / insulin R6 hexamer 1fu2 : FIRST PROTEIN STRUCTURE DETERMINED FROM X-RAY POWDER DIFFRACTION DATA 1fub : FIRST PROTEIN STRUCTURE DETERMINED FROM X-RAY POWDER DIFFRACTION DATA 1g7a : 1.2 A structure of T3R3 human insulin at 100 K 1g7b : 1.3 A STRUCTURE OF T3R3 HUMAN INSULIN AT 100 K 1guj : INSULIN AT PH 2 : STRUCTURAL ANALYSIS OF THE CONDITIONS PROMOTING INSULIN FIBRE FORMATION. 1hiq : PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS 1hit : RECEPTOR BINDING REDEFINED BY A STRUCTURAL SWITCH IN A MUTANT HUMAN INSULIN 1hls : NMR STRUCTURE OF THE HUMAN INSULIN - HIS ( B16 ) 1htv : CRYSTAL STRUCTURE OF DESTRIPEPTIDE ( B28 - B30 ) INSULIN 1iza : ROLE OF B13 GLU IN INSULIN ASSEMBLY : THE HEXAMER STRUCTURE OF RECOMBINANT MUTANT ( B13 GLU - > GLN ) INSULIN 1izb : ROLE OF B13 GLU IN INSULIN ASSEMBLY : THE HEXAMER STRUCTURE OF RECOMBINANT MUTANT ( B13 GLU - > GLN ) INSULIN 1j73 : Crystal structure of an unstable insulin analog with native activity. 1jca : Non-standard Design of Unstable Insulin Analogues with Enhanced Activity 1jco : Solution structure of the monomeric ( Thr ( B27 ) - > Pro, Pro ( B28 ) - > Thr ) insulin mutant ( PT insulin ) 1lph : LYS ( B28 ) PRO ( B29 ) - HUMAN INSULIN 1m5a : Crystal Structure of 2 - Co ( 2 + ) - Insulin at 1.2 A Resolution 1mhi : THREE - DIMENSIONAL SOLUTION STRUCTURE OF AN INSULIN DIMER. A STUDY OF THE B9 ( ASP ) MUTANT OF HUMAN INSULIN USING NUCLEAR MAGNETIC RESONANCE DISTANCE GEOMETRY AND RESTRAINED MOLECULAR DYNAMICS 1mhj : SOLUTION STRUCTURE OF THE SUPERACTIVE MONOMERIC DES - ( PHE ( B25 ) ) HUMAN INSULIN MUTANT. ELUCIDATION OF THE STRUCTURAL BASIS FOR THE MONOMERIZATION OF THE DES - ( PHE ( B25 ) ) INSULIN AND THE DIMERIZATION OF NATIVE INSULIN 1mpj : X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX - STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL 1mso : T6 Human Insulin at 1.0 A Resolution 1os3 : Dehydrated T6 human insulin at 100 K 1os4 : Dehydrated T6 human insulin at 295 K 1q4v : CRYSTAL STRUCTURE OF ALLO - ILEA2 - INSULIN, AN INACTIVE CHIRAL ANALOGUE : IMPLICATIONS FOR THE MECHANISM OF RECEPTOR 1qiy : HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH PHENOL 1qiz : HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH RESORCINOL 1qj0 : HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR 1rwe : Enhancing the activity of insulin at receptor edge : crystal structure and photo - cross-linking of A8 analogues 1sf1 : NMR STRUCTURE OF HUMAN INSULIN under Amyloidogenic Condition, 15 STRUCTURES 1t0c : Solution Structure of Human Proinsulin C - Peptide 1trz : CRYSTALLOGRAPHIC EVIDENCE FOR DUAL COORDINATION AROUND ZINC IN THE T3R3 HUMAN INSULIN HEXAMER 1tyl : THE STRUCTURE OF A COMPLEX OF HEXAMERIC INSULIN AND 4 ' - HYDROXYACETANILIDE 1tym : THE STRUCTURE OF A COMPLEX OF HEXAMERIC INSULIN AND 4 ' - HYDROXYACETANILIDE 1uz9 : CRYSTALLOGRAPHIC AND SOLUTION STUDIES OF N - LITHOCHOLYL INSULIN : A NEW GENERATION OF PROLONGED - ACTING INSULINS. 1w8p : STRUCTURAL PROPERTIES OF THE B25TYR - NME - B26PHE INSULIN MUTANT. 1wav : CRYSTAL STRUCTURE OF FORM B MONOCLINIC CRYSTAL OF INSULIN 1xda : STRUCTURE OF INSULIN 1xgl : HUMAN INSULIN DISULFIDE ISOMER, NMR, 10 STRUCTURES 1xw7 : Diabetes - Associated Mutations in Human Insulin : Crystal Structure and Photo - Cross-Linking Studies of A-Chain Variant Insulin Wakayama 1zeg : STRUCTURE OF B28 ASP INSULIN IN COMPLEX WITH PHENOL 1zeh : STRUCTURE OF INSULIN 1zni : INSULIN 1znj : INSULIN, MONOCLINIC CRYSTAL FORM 2a3g : The structure of T6 bovine insulin 2aiy : R6 HUMAN INSULIN HEXAMER ( SYMMETRIC ), NMR, 20 STRUCTURES 2bn1 : INSULIN AFTER A HIGH DOSE X-RAY BURN 2bn3 : INSULIN BEFORE A HIGH DOSE X-RAY BURN 2c8q : INSULINE ( 1SEC ) AND UV LASER EXCITED FLUORESCENCE 2c8r : INSULINE ( 60SEC ) AND UV LASER EXCITED FLUORESCENCE 2g4m : Insulin collected at 2.0 A wavelength 2g54 : Crystal structure of Zn - bound human insulin - degrading enzyme in complex with insulin B chain 2g56 : crystal structure of human insulin - degrading enzyme in complex with insulin B chain 2hiu : NMR STRUCTURE OF HUMAN INSULIN IN 20 % ACETIC ACID, ZINC - FREE, 10 STRUCTURES 2ins : THE STRUCTURE OF DES - PHE B1 BOVINE INSULIN 2omg : Structure of human insulin cocrystallized with protamine and urea 2omh : Structure of human insulin cocrystallized with ARG - 12 peptide in presence of urea 2omi : Structure of human insulin cocrystallized with protamine 2tci : X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX - STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL 3aiy : R6 HUMAN INSULIN HEXAMER ( SYMMETRIC ), NMR, REFINED AVERAGE STRUCTURE 3ins : STRUCTURE OF INSULIN. RESULTS OF JOINT NEUTRON AND X-RAY REFINEMENT 3mth : X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX - STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL 4aiy : R6 HUMAN INSULIN HEXAMER ( SYMMETRIC ), NMR, ' GREEN ' SUBSTATE, AVERAGE STRUCTURE 4ins : THE STRUCTURE OF 2ZN PIG INSULIN CRYSTALS AT 1.5 ANGSTROMS RESOLUTION 5aiy : R6 HUMAN INSULIN HEXAMER ( SYMMETRIC ), NMR, ' RED ' SUBSTATE, AVERAGE STRUCTURE 6ins : X-RAY ANALYSIS OF THE SINGLE CHAIN / B29 - A1 $ PEPTIDE - LINKED INSULIN MOLECULE. A COMPLETELY INACTIVE ANALOGUE 7ins : STRUCTURE OF PORCINE INSULIN COCRYSTALLIZED WITH CLUPEINE Z 9ins : MONOVALENT CATION BINDING IN CUBIC INSULIN CRYSTALS Hormones Endocrine glands Hypothalamic - pituitary Hypothalamus GnRH TRH Dopamine CRH GHRH Somatostatin ( GHIH ) MCH Posterior pituitary Oxytocin Vasopressin Anterior pituitary FSH LH TSH Prolactin POMC CLIP ACTH MSH Endorphins Lipotropin GH Adrenal axis Adrenal cortex Aldosterone Cortisol Cortisone DHEA DHEA - S Androstenedione Adrenal medulla Epinephrine Norepinephrine Thyroid Thyroid hormones Calcitonin Thyroid axis Parathyroid PTH Gonadal axis Testis Testosterone AMH Inhibin Ovary Estradiol Progesterone Activin Inhibin Relaxin GnSAF Placenta hCG HPL Estrogen Progesterone Pancreas Glucagon Insulin Amylin Somatostatin Pancreatic polypeptide Pineal gland Melatonin N, N - Dimethyltryptamine 5 - Methoxy - N, N - dimethyltryptamine Other Thymus Thymosins Thymosin α1 Beta thymosins Thymopoietin Thymulin Digestive system Stomach Gastrin Ghrelin Duodenum CCK Incretins GIP GLP - 1 Secretin Motilin VIP Ileum Enteroglucagon Peptide YY Liver / other Insulin - like growth factor IGF - 1 IGF - 2 Adipose tissue Leptin Adiponectin Resistin Skeleton Osteocalcin Kidney Renin EPO Calcitriol Prostaglandin Heart Natriuretic peptide ANP BNP Signaling peptide / protein receptor modulators Adiponectin AdipoR Agonists : Peptide : Adiponectin ADP - 355 ADP - 399 ; Non-peptide : AdipoRon ( -- ) - Arctigenin Arctiin Gramine Matairesinol Antagonists : Peptide : ADP - 400 AdipoR Agonists : Peptide : Adiponectin ADP - 355 ADP - 399 ; Non-peptide : AdipoRon Deoxyschizandrin Parthenolide Syringing Taxifoliol Antagonists : Peptide : ADP - 400 Angiotensin See here instead. Bradykinin Agonists : Bradykinin Kallidin Antagonists : FR - 173657 Icatibant LF22 - 0542 CGRP Agonists : Amylin CGRP Pramlintide Antagonists : Atogepant BI 44370 TA CGRP ( 8 - 37 ) MK - 3207 Olcegepant Rimegepant SB - 268262 Telcagepant Ubrogepant Antibodies : Eptinezumab Erenumab Fremanezumab Galcanezumab Cholecystokinin CCK Agonists : Cholecystokinin Antagonists : Amiglumide Asperlicin Devazepide Dexloxiglumide Lintitript Lorglumide Loxiglumide Pranazepide Proglumide Tarazepide Tomoglumide CCK Agonists : Cholecystokinin CCK - 4 Gastrin Pentagastrin ( CCK - 5 ) Antagonists : Ceclazepide CI - 988 ( PD - 134308 ) Itriglumide L - 365,360 Netazepide Proglumide Spiroglumide Unsorted Antagonists : Nastorazepide CRH CRF Agonists : Cortagine Corticorelin Corticotropin releasing hormone Sauvagine Stressin I Urocortin Antagonists : Antalarmin Astressin - B CP - 154,526 Emicerfont Hypericin LWH - 234 NBI - 27914 NBI - 74788 Pexacerfont R - 121919 TS - 041 Verucerfont CRF Agonists : Corticorelin Corticotropin releasing hormone Sauvagine Urocortin Antagonists : Astressin - B Cytokine See here instead. Endothelin Agonists : Endothelin 1 Endothelin 2 Endothelin 3 IRL - 1620 Antagonists : A-192621 ACT - 132577 Ambrisentan Aprocitentan Atrasentan Avosentan Bosentan BQ - 123 BQ - 788 Clazosentan Darusentan Edonentan Enrasentan Fandosentan Feloprentan Macitentan Nebentan Sitaxentan Sparsentan Tezosentan Zibotentan Galanin GAL Agonists : Galanin Galanin ( 1 - 15 ) Galanin - like peptide Galmic Galnon NAX 810 - 2 Antagonists : C7 Dithiepine - 1, 1, 4, 4 - tetroxide Galantide ( M15 ) M32 M35 M40 SCH - 202596 GAL Agonists : Galanin Galanin ( 1 - 15 ) Galanin ( 2 - 11 ) Galanin - like peptide Galmic Galnon J18 NAX 810 - 2 Antagonists : C7 Galantide ( M15 ) M32 M35 M40 M871 GAL Agonists : Galanin Galanin ( 1 - 15 ) Galmic Galnon Antagonists : C7 Galantide ( M15 ) GalR3ant HT - 2157 M32 M35 M40 SNAP - 37889 SNAP - 398299 Ghrelin / GHS See here instead. GH See here instead. GHRH See here instead. GLP GLP - 1 Agonists : Albiglutide Beinaglutide Dulaglutide Efpeglenatide Exenatide GLP - 1 Langlenatide Liraglutide Lixisenatide Oxyntomodulin Pegapamodutide Semaglutide Taspoglutide GLP - 2 Agonists : Apraglutide Elsiglutide Glepaglutide GLP - 2 Teduglutide Others Propeptides : Preproglucagon Proglucagon Glucagon Agonists : Dasiglucagon Glucagon Oxyntomodulin Antagonists : Adomeglivant L - 168,049 LGD - 6972 Propeptides : Preproglucagon Proglucagon GnRH See here instead. Gonadotropin See here instead. Growth factor See here instead. Insulin Agonists : Chaetochromin ( 4548 - G05 ) Insulin - like growth factor 1 Insulin - like growth factor 2 Insulin Insulin aspart Insulin degludec Insulin detemir Insulin glargine Insulin glulisine Insulin lispro Mecasermin Mecasermin rinfabate Antagonists : BMS - 754807 S661 S961 Kinase inhibitors : Linsitinib Antibodies : Xentuzumab ( against IGF - 1 and IGF - 2 ) Kisspeptin Agonists : Kisspeptin Kisspeptin - 10 Antagonists : Kisspeptin - 234 Leptin Agonists : Leptin Metreleptin MCH MCH Agonists : Melanin concentrating hormone Antagonists : ATC - 0065 ATC - 0175 GW - 803430 NGD - 4715 SNAP - 7941 SNAP - 94847 MCH Agonists : Melanin concentrating hormone Melanocortin See here instead. Neuropeptide FF Agonists : Neuropeptide AF Neuropeptide FF Neuropeptide SF ( RFRP - 1 ) Neuropeptide VF ( RFRP - 3 ) Antagonists : BIBP - 3226 RF9 Neuropeptide S Agonists : Neuropeptide S Antagonists : ML - 154 SHA - 68 Neuropeptide Y Y Agonists : Neuropeptide Y Peptide YY Antagonists : BIBO - 3304 BIBP - 3226 BVD - 10 GR - 231118 PD - 160170 Y Agonists : 2 - Thiouridine 5 ' - triphosphate Neuropeptide Y Neuropeptide Y ( 13 - 36 ) Peptide YY Peptide YY ( 3 - 36 ) Antagonists : BIIE - 0246 JNJ - 5207787 SF - 11 Y Agonists : GR - 231118 Neuropeptide Y Pancreatic polypeptide Peptide YY Antagonists : UR - AK49 Y Agonists : BWX - 46 Neuropeptide Y Peptide YY Antagonists : CGP - 71683 FMS - 586 L - 152,804 Lu AA - 33810 MK - 0557 NTNCB Velneperit ( S - 2367 ) Neurotensin NTS Agonists : Neurotensin Neuromedin N Antagonists : Meclinertant SR - 142948 NTS Agonists : Neurotensin Antagonists : Levocabastine SR - 142948 Opioid See here instead. Orexin OX Agonists : Orexin ( A, B) Antagonists : ACT - 335827 ACT - 462206 Almorexant Filorexant Lemborexant Nemorexant RTIOX - 276 SB - 334867 SB - 408124 SB - 649868 Suvorexant TCS - 1102 OX Agonists : Orexin ( A, B) SB - 668875 Antagonists : ACT - 335827 ACT - 462206 Almorexant EMPA Filorexant JNJ - 10397049 Lemborexant MK - 1064 SB - 649868 Seltorexant Suvorexant TCS - 1102 TCS - OX2 - 29 Oxytocin See here instead. Prolactin Agonists : Growth hormone Human placental lactogen Placental growth hormone ( growth hormone variant ) Prolactin S179D - hPRL Somatotropin Antagonists : Δ1 -- 9 - G129R - hPRL Δ1 -- 14 - G129R - hPRL G120K - hGH G129R - hPRL Prolactin modulators : Prolactin inhibitors : D receptor agonists ( e.g., bromocriptine, cabergoline ) ; Prolactin releasers : D receptor antagonists ( e.g., domperidone, metoclopramide, risperidone ) Estrogens ( e.g., estradiol ) Progestogens ( e.g., progesterone ) PTH Agonists : Abaloparatide Parathyroid hormone Parathyroid hormone - related protein ( PTHrP ) Semparatide Teriparatide Relaxin Agonists : Insulin - like factor 3 Relaxin ( 1, 2, 3 ) Serelaxin Somatostatin See here instead. Tachykinin See here instead. TRH Agonists : Azetirelin Fertirelin Montirelin Orotirelin Posatirelin Protirelin Rovatirelin Taltirelin TRH ( TRF ) TSH Agonists : Thyrotropin alfa TSH ( thyrotropin ) Vasopressin See here instead. VIP / PACAP VIPR Agonists : Peptide : Bay 55 - 9837 LBT - 3393 PACAP VIP VIPR Agonists : Peptide : LBT - 3627 PACAP VIP PAC Agonists : PACAP PACAP ( 1 - 27 ) PACAP ( 1 - 38 ) Antagonists : PACAP ( 6 - 38 ) Unsorted PHI PHM PHV Others Endogenous : Adrenomedullin Apelin Asprosin Bombesin Calcitonin Carnosine CART CLIP DSIP Enteroglucagon Formyl peptide GALP GIP GRP Integrin ligands ( collagens, fibrinogen, fibronectin, laminins, ICAM - 1, ICAM - 2, osteopontin, VCAM - 1, vitronectin ) Kininogens Motilin Natriuretic peptides ( ANP, BNP, CNP, urodilatin ) Nesfatin - 1 Neuromedin B Neuromedin N Neuromedin S Neuromedin U Obestatin Osteocalcin Resistin Secretin Thymopoietin Thymosins Thymulin Urotensin - II VGF Exogenous : Lifitegrast ( LFA - 1 antagonist ) See also Receptor / signaling modulators Growth factor receptor modulators Angiopoietin Agonists : Angiopoietin 1 Angiopoietin 4 Antagonists : Angiopoietin 2 Angiopoietin 3 Kinase inhibitors : Altiratinib CE - 245677 Rebastinib Antibodies : Evinacumab ( against angiopoietin 3 ) Nesvacumab ( against angiopoietin 2 ) CNTF Agonists : Axokine CNTF Dapiclermin EGF ( ErbB ) EGF ( ErbB1 / HER1 ) Agonists : Amphiregulin Betacellulin EGF ( urogastrone ) Epigen Epiregulin Heparin - binding EGF - like growth factor ( HB - EGF ) Murodermin Nepidermin Transforming growth factor alpha ( TGFα ) Kinase inhibitors : Afatinib AG - 490 Agerafenib Brigatinib Canertinib Dacomitinib Erlotinib Gefitinib Grandinin Icotinib Lapatinib Neratinib Osimertinib Vandetanib WHI - P 154 Antibodies : Cetuximab Depatuxizumab Depatuxizumab mafodotin Futuximab Imgatuzumab Matuzumab Necitumumab Nimotuzumab Panitumumab Zalutumumab ErbB2 / HER2 Agonists : Unknown / none Antibodies : Ertumaxomab Pertuzumab Trastuzumab Trastuzumab duocarmazine Trastuzumab emtansine Kinase inhibitors : Afatinib AG - 490 Lapatinib Mubritinib Neratinib ErbB3 / HER3 Agonists : Neuregulins ( heregulins ) ( 1, 2, 6 ( neuroglycan C ) ) Antibodies : Duligotumab Patritumab Seribantumab ErbB4 / HER4 Agonists : Betacellulin Epigen Heparin - binding EGF - like growth factor ( HB - EGF ) Neuregulins ( heregulins ) ( 1, 2, 3, 4, 5 ( tomoregulin, TMEFF ) ) FGF FGFR1 Agonists : Ersofermin FGF ( 1, 2 ( bFGF ), 3, 4, 5, 6, 8, 10 ( KGF2 ), 20 ) Repifermin Trafermin Velafermin FGFR2 Agonists : Ersofermin FGF ( 1, 2 ( bFGF ), 3, 4, 5, 6, 7 ( KGF ), 8, 9, 10 ( KGF2 ), 17, 18, 22 ) Palifermin Repifermin Sprifermin Trafermin Antibodies : Aprutumab Aprutumab ixadotin FGFR3 Agonists : Ersofermin FGF ( 1, 2 ( bFGF ), 4, 8, 9, 18, 23 ) Sprifermin Trafermin Antibodies : Burosumab ( against FGF23 ) FGFR4 Agonists : Ersofermin FGF ( 1, 2 ( bFGF ), 4, 6, 8, 9, 19 ) Trafermin Unsorted Agonists : FGF15 / 19 HGF ( c - Met ) Agonists : Hepatocyte growth factor Potentiators : Dihexa ( PNB - 0408 ) Kinase inhibitors : Altiratinib AM7 AMG - 458 Amuvatinib BMS - 777607 Cabozantinib Crizotinib Foretinib Golvatinib INCB28060 JNJ - 38877605 K252a MK - 2461 PF - 04217903 PF - 2341066 PHA - 665752 SU - 11274 Tivantinib Volitinib Antibodies : Emibetuzumab Ficlatuzumab Flanvotumab Onartuzumab Rilotumumab Telisotuzumab Telisotuzumab vedotin IGF IGF - 1 Agonists : des ( 1 - 3 ) IGF - 1 Insulin - like growth factor - 1 ( somatomedin C ) IGF - 1 LR3 Insulin - like growth factor - 2 ( somatomedin A ) Insulin Mecasermin Mecasermin rinfabate Kinase inhibitors : BMS - 754807 Linsitinib NVP - ADW742 NVP - AEW541 OSl - 906 Antibodies : AVE - 1642 Cixutumumab Dalotuzumab Figitumumab Ganitumab Robatumumab R1507 Teprotumumab Xentuzumab ( against IGF - 1 and IGF - 2 ) IGF - 2 Agonists : Insulin - like growth factor - 2 ( somatomedin A ) Antibodies : Dusigitumab Xentuzumab ( against IGF - 1 and IGF - 2 ) Others Binding proteins : IGFBP ( 1, 2, 3, 4, 5, 6, 7 ) Cleavage products / derivatives with unknown target : Glypromate ( GPE, ( 1 - 3 ) IGF - 1 ) Trofinetide LNGF ( p75 ) Agonists : BDNF BNN - 20 BNN - 27 Cenegermin DHEA DHEA - S NGF NT - 3 NT - 4 Antagonists : ALE - 0540 Dexamethasone EVT - 901 ( SAR - 127963 ) Testosterone Antibodies : Against NGF : ABT - 110 ( PG110 ) ASP - 6294 Fasinumab Frunevetmab Fulranumab MEDI - 578 Ranevetmab Tanezumab Aptamers : Against NGF : RBM - 004 Decoy receptors : LEVI - 04 ( p75 - Fc ) PDGF Agonists : Becaplermin Platelet - derived growth factor ( A, B, C, D ) Kinase inhibitors : Agerafenib Axitinib Crenolanib Imatinib Lenvatinib Masitinib Motesanib Nintedanib Pazopanib Radotinib Quizartinib Sunitinib Sorafenib Toceranib Antibodies : Olaratumab Ramucirumab Tovetumab RET ( GFL ) GFRα1 Agonists : Glial cell line - derived neurotrophic factor ( GDNF ) Liatermin Kinase inhibitors : Vandetanib GFRα2 Agonists : Neurturin ( NRTN ) Kinase inhibitors : Vandetanib GFRα3 Agonists : Artemin ( ARTN ) Kinase inhibitors : Vandetanib GFRα4 Agonists : Persephin ( PSPN ) Kinase inhibitors : Vandetanib Unsorted Kinase inhibitors : Agerafenib SCF ( c - Kit ) Agonists : Ancestim Stem cell factor Kinase inhibitors : Agerafenib Axitinib Dasatinib Imatinib Masitinib Nilotinib Pazopanib Quizartinib Sorafenib Sunitinib Toceranib TGFβ See here instead. Trk TrkA Agonists : Amitriptyline BNN - 20 BNN - 27 Cenegermin DHEA DHEA - S Gambogic amide NGF Tavilermide Antagonists : ALE - 0540 Dexamethasone FX007 Testosterone Negative allosteric modulators : VM - 902A Kinase inhibitors : Altiratinib AZD - 6918 CE - 245677 CH - 7057288 DS - 6051 Entrectinib GZ - 389988 K252a Larotrectinib Lestaurtinib Milciclib ONO - 4474 ONO - 5390556 PLX - 7486 Rebastinib SNA - 120 ( pegylated K252a ) ) Antibodies : Against TrkA : GBR - 900 ; Against NGF : ABT - 110 ( PG110 ) ASP - 6294 Fasinumab Frunevetmab Fulranumab MEDI - 578 Ranevetmab Tanezumab Aptamers : Against NGF : RBM - 004 Decoy receptors : ReN - 1820 ( TrkAd5 ) TrkB Agonists : 3, 7 - DHF 3, 7, 8, 2 ' - THF 4 ' - DMA - 7, 8 - DHF 7, 3 ' - DHF 7, 8 - DHF 7, 8, 2 ' - THF 7, 8, 3 ' - THF Amitriptyline BDNF BNN - 20 Deoxygedunin Deprenyl Diosmetin DMAQ - B1 HIOC LM22A - 4 N - Acetylserotonin NT - 3 NT - 4 Norwogonin ( 5, 7, 8 - THF ) R7 R13 TDP6 Antagonists : ANA - 12 Cyclotraxin B Gossypetin ( 3, 5, 7, 8, 3 ', 4 ' - HHF ) Ligands : DHEA Kinase inhibitors : Altiratinib AZD - 6918 CE - 245677 CH - 7057288 DS - 6051 Entrectinib GZ - 389988 K252a Larotrectinib Lestaurtinib ONO - 4474 ONO - 5390556 PLX - 7486 TrkC Agonists : BNN - 20 DHEA NT - 3 Kinase inhibitors : Altiratinib AZD - 6918 CE - 245677 CH - 7057288 DS - 6051 Entrectinib GZ - 389988 K252a Larotrectinib Lestaurtinib ONO - 4474 ONO - 5390556 PLX - 7486 VEGF Agonists : Placental growth factor ( PGF ) Telbermin VEGF ( A, B, C, D ( FIGF ) ) Allosteric modulators : Cyclotraxin B Kinase inhibitors : Agerafenib Altiratinib Axitinib Cabozantinib Cediranib Lapatinib Lenvatinib Motesanib Nintedanib Pazopanib Pegaptanib Rebastinib Regorafenib Semaxanib Sorafenib Sunitinib Toceranib Tivozanib Vandetanib WHI - P 154 Antibodies : Alacizumab pegol Bevacizumab Icrucumab Ramucirumab Ranibizumab Decoy receptors : Aflibercept Others Additional growth factors : Adrenomedullin Colony - stimulating factors ( see here instead ) Connective tissue growth factor ( CTGF ) Ephrins ( A1, A2, A3, A4, A5, B1, B2, B3 ) Erythropoietin ( see here instead ) Glucose - 6 - phosphate isomerase ( GPI ; PGI, PHI, AMF ) Glia maturation factor ( GMF ) Hepatoma - derived growth factor ( HDGF ) Interleukins / T - cell growth factors ( see here instead ) Leukemia inhibitory factor ( LIF ) Macrophage - stimulating protein ( MSP ; HLP, HGFLP ) Midkine ( NEGF2 ) Migration - stimulating factor ( MSF ; PRG4 ) Oncomodulin Pituitary adenylate cyclase - activating peptide ( PACAP ) Pleiotrophin Renalase Thrombopoietin ( see here instead ) Wnt signaling proteins Additional growth factor receptor modulators : Cerebrolysin ( neurotrophin mixture ) See also Receptor / signaling modulators Signaling peptide / protein receptor modulators Cytokine receptor modulators Retrieved from `` https://en.wikipedia.org/w/index.php?title=Insulin&oldid=864223477 '' Categories : Genes on human chromosome 11 Animal products Eli Lilly and Company Hormones of glucose metabolism Human hormones Insulin receptor agonists Insulin therapies Insulin - like growth factor receptor agonists Pancreatic hormones Peptide hormones Recombinant proteins Tumor markers World Anti-Doping Agency prohibited substances Hidden categories : CS1 Swedish - language sources ( sv ) Webarchive template wayback links CS1 French - language sources ( fr ) CS1 : Julian -- Gregorian uncertainty CS1 maint : Unrecognized language All articles with unsourced statements Articles with unsourced statements from March 2017 Articles needing additional references from July 2018 All articles needing additional references Articles with unsourced statements from April 2015 Talk Contents About Wikipedia Afrikaans অসমীয়া Asturianu Azərbaycanca বাংলা Беларуская Беларуская ( тарашкевіца ) ‎ Български Boarisch Bosanski Català Čeština Cymraeg Dansk Deutsch ދިވެހިބަސް Eesti Ελληνικά Español Esperanto Euskara فارسی Français Gaeilge Galego 한국어 Հայերեն हिन्दी Hrvatski Ido Bahasa Indonesia Interlingua Íslenska Italiano עברית Basa Jawa ಕನ್ನಡ Kapampangan Қазақша Kurdî Кыргызча Latina Latviešu Lietuvių Magyar Македонски മലയാളം Bahasa Melayu မြန်မာဘာသာ Nederlands 日本 語 Norsk Norsk nynorsk Occitan Oʻzbekcha / ўзбекча ਪੰਜਾਬੀ پنجابی پښتو Polski Português Română Русский Scots Shqip Simple English Slovenčina Slovenščina کوردی Српски / srpski Srpskohrvatski / српскохрватски Basa Sunda Suomi Svenska தமிழ் ไทย Türkçe Українська اردو Tiếng Việt Winaray 吴语 ייִדיש 粵語 中文 76 more Edit links This page was last edited on 15 October 2018, at 22 : 06 ( UTC ). 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Question: where is insulin stored in the human body
Answer: pancreas