Glucagon - wikipedia Glucagon This article is about the natural hormone. For the medication, see Glucagon ( medication ). GCG Available structures PDB Human UniProt search : PDBe RCSB List of PDB id codes 1BH0, 1D0R, 1NAU, 2G49, 2L63, 2L64, 2M5P, 2M5Q, 3IOL, 4APD, 4ZGM Identifiers Aliases GCG, GLP1, GLP2, GRPP, glucagon, Glucagon, GLP - 1, GLP External IDs OMIM : 138030 HomoloGene : 136497 GeneCards : GCG Gene location ( Human ) Chr. Chromosome 2 ( human ) Band 2q24. 2 Start 162,142,873 bp End 162,152,404 bp RNA expression pattern More reference expression data Gene ontology Molecular function protein binding identical protein binding receptor binding hormone activity glucagon receptor binding Cellular component cytoplasm endoplasmic reticulum lumen plasma membrane extracellular region secretory granule lumen extracellular space Biological process negative regulation of execution phase of apoptosis G - protein coupled receptor signaling pathway regulation of insulin secretion cellular response to glucagon stimulus positive regulation of peptidyl - serine phosphorylation positive regulation of calcium ion import positive regulation of histone H3 - K4 methylation positive regulation of peptidyl - threonine phosphorylation feeding behavior positive regulation of ERK1 and ERK2 cascade positive regulation of protein binding cell proliferation positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter signal transduction positive regulation of protein kinase activity adenylate cyclase - modulating G - protein coupled receptor signaling pathway protein kinase A signaling positive regulation of insulin secretion involved in cellular response to glucose stimulus response to starvation negative regulation of apoptotic process regulation of receptor activity adenylate cyclase - activating G - protein coupled receptor signaling pathway Sources : Amigo / QuickGO Orthologs Species Human Mouse Entrez 2641 n / a Ensembl ENSG00000115263 n / a UniProt P01275 n / a RefSeq ( mRNA ) NM_002054 n / a RefSeq ( protein ) NP_002045 n / a Location ( UCSC ) Chr 2 : 162.14 -- 162.15 Mb n / a PubMed search n / a Wikidata View / Edit Human Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It works to raise the concentration of glucose and fat in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a medication to treat a number of health conditions. Its effect is opposite to that of insulin, which lowers the extracellular glucose. The pancreas releases glucagon when the concentration of glucose in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream. High blood - glucose levels, on the other hand, stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulin - dependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. Glucagon increases energy expenditure and is elevated under conditions of stress. Glucagon belongs to the secretin family of hormones. Contents 1 Function 2 Mechanism of action 3 Physiology 3.1 Production 3.2 Regulation 4 Structure 5 Pathology 6 History 6.1 Etymology 7 See also 8 References Function Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis. Glucagon also decreases fatty acid synthesis in adipose tissue and the liver, as well as promoting lipolysis in these tissues, which causes them to release fatty acids into circulation where they can be catabolised to generate energy in tissues such as skeletal muscle when required. Glucose is stored in the liver in the form of the polysaccharide glycogen, which is a glucan ( a polymer made up of glucose molecules ). Liver cells ( hepatocytes ) have glucagon receptors. When glucagon binds to the glucagon receptors, the liver cells convert the glycogen into individual glucose molecules and release them into the bloodstream, in a process known as glycogenolysis. As these stores become depleted, glucagon then encourages the liver and kidney to synthesize additional glucose by gluconeogenesis. Glucagon turns off glycolysis in the liver, causing glycolytic intermediates to be shuttled to gluconeogenesis. Glucagon also regulates the rate of glucose production through lipolysis. Glucagon induces lipolysis in humans under conditions of insulin suppression ( such as diabetes mellitus type 1 ). Glucagon production appears to be dependent on the central nervous system through pathways yet to be defined. In invertebrate animals, eyestalk removal has been reported to affect glucagon production. Excising the eyestalk in young crayfish produces glucagon - induced hyperglycemia. Mechanism of action Metabolic regulation of glycogen by glucagon. Glucagon binds to the glucagon receptor, a G protein - coupled receptor, located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. When the G protein interacts with the receptor, it undergoes a conformational change that results in the replacement of the GDP molecule that was bound to the α subunit with a GTP molecule. This substitution results in the releasing of the α subunit from the β and γ subunits. The alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase. Adenylate cyclase manufactures cyclic adenosine monophosphate ( cyclic AMP or cAMP ), which activates protein kinase A ( cAMP - dependent protein kinase ). This enzyme, in turn, activates phosphorylase kinase, which then phosphorylates glycogen phosphorylase b ( PYG b ), converting it into the active form called phosphorylase a ( PYG a ). Phosphorylase a is the enzyme responsible for the release of glucose - 1 - phosphate from glycogen polymers. Additionally, the coordinated control of glycolysis and gluconeogenesis in the liver is adjusted by the phosphorylation state of the enzymes that catalyze the formation of a potent activator of glycolysis called fructose - 2, 6 - bisphosphate. The enzyme protein kinase A that was stimulated by the cascade initiated by glucagon will also phosphorylate a single serine residue of the bifunctional polypeptide chain containing both the enzymes fructose - 2, 6 - bisphosphatase and phosphofructokinase - 2. This covalent phosphorylation initiated by glucagon activates the former and inhibits the latter. This regulates the reaction catalyzing fructose - 2, 6 - bisphosphate ( a potent activator of phosphofructokinase - 1, the enzyme that is the primary regulatory step of glycolysis ) by slowing the rate of its formation, thereby inhibiting the flux of the glycolysis pathway and allowing gluconeogenesis to predominate. This process is reversible in the absence of glucagon ( and thus, the presence of insulin ). Glucagon stimulation of PKA also inactivates the glycolytic enzyme pyruvate kinase in hepatocytes. Physiology Production A microscopic image stained for glucagon The hormone is synthesized and secreted from alpha cells ( α - cells ) of the islets of Langerhans, which are located in the endocrine portion of the pancreas. Production, which is otherwise freerunning, is suppressed / regulated by insulin from the adjacent beta cells. When blood sugar drops, insulin production drops and more glucagon is produced In rodents, the alpha cells are located in the outer rim of the islet. Human islet structure is much less segregated, and alpha cells are distributed throughout the islet in close proximity to beta cells. Glucagon is also produced by alpha cells in the stomach. Recent research has demonstrated that glucagon production may also take place outside the pancreas, with the gut being the most likely site of extrapancreatic glucagon synthesis. Regulation Secretion of glucagon is stimulated by : Hypoglycemia Epinephrine ( via β2, α2, and α1 adrenergic receptors ) Arginine Alanine ( often from muscle - derived pyruvate / glutamate transamination ( see alanine transaminase reaction ). Acetylcholine Cholecystokinin Secretion of glucagon is inhibited by : Somatostatin Insulin ( via GABA ) PPARγ / retinoid X receptor heterodimer. Increased free fatty acids and keto acids into the blood. Increased urea production Structure Glucagon is a 29 - amino acid polypeptide. Its primary structure in humans is : NH - His - Ser - Gln - Gly - Thr - Phe - Thr - Ser - Asp - Tyr - Ser - Lys - Tyr - Leu - Asp - Ser - Arg - Arg - Ala - Gln - Asp - Phe - Val - Gln - Trp - Leu - Met - Asn - Thr - COOH. The polypeptide has a molecular weight of 3485 daltons. Glucagon is a peptide ( non steroid ) hormone. Glucagon is generated from the cleavage of proglucagon by proprotein convertase 2 in pancreatic islet α cells. In intestinal L cells, proglucagon is cleaved to the alternate products glicentin, GLP - 1 ( an incretin ), IP - 2, and GLP - 2 ( promotes intestinal growth ). Pathology Abnormally elevated levels of glucagon may be caused by pancreatic tumors, such as glucagonoma, symptoms of which include necrolytic migratory erythema, reduced amino acids, and hyperglycemia. It may occur alone or in the context of multiple endocrine neoplasia type 1. History In the 1920s, Kimball and Murlin studied pancreatic extracts, and found an additional substance with hyperglycemic properties. They described glucagon in 1923. The amino acid sequence of glucagon was described in the late 1950s. A more complete understanding of its role in physiology and disease was not established until the 1970s, when a specific radioimmunoassay was developed. Etymology Kimball and Murlin coined the term glucagon in 1923 when they initially named the substance the glucose agonist. See also Cortisol Diabetes mellitus Glucagon - like peptide - 1 Glucagon - like peptide - 2 Insulin Islets of Langerhans Pancreas Proglucagon Tyrosine kinase References ^ Jump up to : GRCh38 : Ensembl release 89 : ENSG00000115263 - Ensembl, May 2017 Jump up ^ `` Human PubMed Reference : ''. Jump up ^ Voet D, Voet JG. ( 2011 ). Biochemistry ( 4th ed. ). New York : Wiley. Jump up ^ Reece J, Campbell N ( 2002 ). Biology. San Francisco : Benjamin Cummings. ISBN 0 - 8053 - 6624 - 5. Jump up ^ Orsay J ( 2014 ). Biology 1 : Molecules. Examkrackers Inc. p. 77. ISBN 978 - 1 - 893858 - 70 - 1. Jump up ^ Jones BJ, Tan T, Bloom SR ( March 2012 ). `` Minireview : Glucagon in stress and energy homeostasis ''. Endocrinology. 153 ( 3 ) : 1049 -- 54. doi : 10.1210 / en. 2011 - 1979. PMC 3281544. PMID 22294753. Jump up ^ Voet D, Voet JG ( 2011 ). Biochemistry ( 4th ed. ). New York : Wiley. Jump up ^ HABEGGER, K.M., HEPPNER, K.M., GEARY, N., BARTNESS, T.J., DIMARCHI, R. & TSCHÖP, M.H. ( 2010 ). `` The metabolic actions of glucagon revisited ''. Nature reviews. Endocrinology. 6 : 689 -- 697. doi : 10.1038 / nrendo. 2010.187. CS1 maint : Multiple names : authors list ( link ) Jump up ^ Liljenquist JE, Bomboy JD, Lewis SB, Sinclair - Smith BC, Felts PW, Lacy WW, Crofford OB, Liddle GW ( January 1974 ). `` Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men '' ( PDF ). The Journal of Clinical Investigation. 53 ( 1 ) : 190 -- 7. doi : 10.1172 / JCI107537. PMC 301453. PMID 4808635. Jump up ^ Leinen RL, Giannini AJ ( 1983 ). `` Effect of eyestalk removal on glucagon induced hyperglycemia in crayfish ''. Society for Neuroscience Abstracts. 9 : 604. Jump up ^ Hue L, Rider MH ( July 1987 ). `` Role of fructose 2, 6 - bisphosphate in the control of glycolysis in mammalian tissues ''. The Biochemical Journal. 245 ( 2 ) : 313 -- 24. PMC 1148124. PMID 2822019. Jump up ^ Claus TH, El - Maghrabi MR, Regen DM, Stewart HB, McGrane M, Kountz PD, Nyfeler F, Pilkis J, Pilkis SJ ( 1984 ). `` The role of fructose 2, 6 - bisphosphate in the regulation of carbohydrate metabolism ''. Current Topics in Cellular Regulation. 23 : 57 -- 86. doi : 10.1016 / b978 - 0 - 12 - 152823 - 2.50006 - 4. PMID 6327193. Jump up ^ Feliú JE, Hue L, Hers HG ( August 1976 ). `` Hormonal control of pyruvate kinase activity and of gluconeogenesis in isolated hepatocytes ''. Proceedings of the National Academy of Sciences of the United States of America. 73 ( 8 ) : 2762 -- 6. doi : 10.1073 / pnas. 73.8. 2762. PMC 430732. PMID 183209. ^ Jump up to : Unger RH, Cherrington AD ( January 2012 ). `` Glucagonocentric restructuring of diabetes : a pathophysiologic and therapeutic makeover ''. The Journal of Clinical Investigation. 122 ( 1 ) : 4 -- 12. doi : 10.1172 / JCI60016. PMC 3248306. PMID 22214853. Jump up ^ Holst JJ, Holland W, Gromada J, Lee Y, Unger RH, Yan H, Sloop KW, Kieffer TJ, Damond N, Herrera PL ( April 2017 ). `` Insulin and Glucagon : Partners for Life ''. Endocrinology. 158 ( 4 ) : 696 -- 701. doi : 10.1210 / en. 2016 - 1748. PMID 28323959. Jump up ^ Layden BT, Durai V, Lowe WL ( 2010 ). `` G - Protein - Coupled Receptors, Pancreatic Islets, and Diabetes ''. Nature Education. 3 ( 9 ) : 13. Jump up ^ Skoglund G, Lundquist I, Ahrén B ( November 1987 ). `` Alpha 1 - and alpha 2 - adrenoceptor activation increases plasma glucagon levels in the mouse ''. European Journal of Pharmacology. 143 ( 1 ) : 83 -- 8. doi : 10.1016 / 0014 - 2999 ( 87 ) 90737 - 0. PMID 2891547. Jump up ^ Honey RN, Weir GC ( October 1980 ). `` Acetylcholine stimulates insulin, glucagon, and somatostatin release in the perfused chicken pancreas ''. Endocrinology. 107 ( 4 ) : 1065 -- 8. doi : 10.1210 / endo - 107 - 4 - 1065. PMID 6105951. Jump up ^ Xu E, Kumar M, Zhang Y, Ju W, Obata T, Zhang N, Liu S, Wendt A, Deng S, Ebina Y, Wheeler MB, Braun M, Wang Q ( January 2006 ). `` Intra-islet insulin suppresses glucagon release via GABA - GABAA receptor system ''. Cell Metabolism. 3 ( 1 ) : 47 -- 58. doi : 10.1016 / j. cmet. 2005.11. 015. PMID 16399504. Jump up ^ Krätzner R, Fröhlich F, Lepler K, Schröder M, Röher K, Dickel C, Tzvetkov MV, Quentin T, Oetjen E, Knepel W ( February 2008 ). `` A peroxisome proliferator - activated receptor gamma - retinoid X receptor heterodimer physically interacts with the transcriptional activator PAX6 to inhibit glucagon gene transcription ''. Molecular Pharmacology. 73 ( 2 ) : 509 -- 17. doi : 10.1124 / mol. 107.035568. PMID 17962386. Jump up ^ Johnson LR ( 2003 ). Essential Medical Physiology. Academic Press. pp. 643 --. ISBN 978 - 0 - 12 - 387584 - 6. Jump up ^ Unger RH, Orci L ( June 1981 ). `` Glucagon and the A cell : physiology and pathophysiology ( first two parts ) ''. The New England Journal of Medicine. 304 ( 25 ) : 1518 -- 24. doi : 10.1056 / NEJM198106183042504. PMID 7015132. Jump up ^ Orskov C, Holst JJ, Poulsen SS, Kirkegaard P ( November 1987 ). `` Pancreatic and intestinal processing of proglucagon in man ''. Diabetologia. 30 ( 11 ) : 874 -- 81. doi : 10.1007 / BF00274797. PMID 3446554. Jump up ^ Kimball C, Murlin J ( 1923 ). `` Aqueous extracts of pancreas III. Some precipitation reactions of insulin ''. J. Biol. Chem. 58 ( 1 ) : 337 -- 348. Jump up ^ Bromer W, Winn L, Behrens O ( 1957 ). `` The amino acid sequence of glucagon V. Location of amide groups, acid degradation studies and summary of sequential evidence ''. J. Am. Chem. Soc. 79 ( 11 ) : 2807 -- 2810. doi : 10.1021 / ja01568a038. Jump up ^ `` History of glucagon - Metabolism, insulin and other hormones - Diapedia, The Living Textbook of Diabetes ''. www.diapedia.org. Retrieved 2017 - 03 - 26. 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Question: high blood glucose levels stimulate the release of
Answer: insulin