add extra information in the meddile of these , i prefer if i can use it to buld on the information of some one when he say somthing of those and i prefer if its clinicl . i want the information to not be mintind in my text . 
synthesis, structure, and release of insulin
• •Insulin is a peptide hormone produced by the β cell of the islets of
Langerhans.
• • Insulin is composed of 51 amino acids arranged in two polypeptide
Chains, designated A ( 21 AA) and B (30 AA), which are linked together by
two disulfide bonds.
Synthesis of insulin:
• Biosynthesis involves the production of two inactive precursors, preproinsulin and proinsulin, which are sequentially cleaved to form the active
hormone plus the C- peptides in a 1:1 ratio
•Insulin is synthesized as a long polypeptide of 110 AA (Pre-proinsulin)
• Signal sequence at N terminal end of pre-proinsulin are cleaved in ER to
form pro-insulin, pro-insulin is transferred to the Golgi apparatus where it
undergoes proteolysis to give insulin and C-peptide
• In the Golgi apparatus insulin combines with zinc and is packaged into
secretory granules (zinc is essential for insulin activity)
• Both insulin and C-peptide are secreted into the circulation
• Insulin stimulates phosphoprotein of the phosphatase enzyme that
dephosphorylates glycogen synthase (activate it )and glycogen
phosphorylase (inactivate it)
C-peptide :
• Is essential for proper insulin folding.
• Also, because its half-life in plasma is longer than that of insulin, c-peptide
level is a good indicator of insulin production and secretion.
•Insulin has a plasma half-life of 6 minutes.
Secretion of insulin

Increased secretion
a) Glucose (Ingestion of a carbohydrate-rich meal leads to a rise in blood glucose,
the primary stimulus for insulin secretion)
• b) Amino acids ( Ingestion of protein causes a transient rise in plasma amino acid
levels (for example, arginine) that enhances the glucose-stimulated secretion of
insulin. [Note: Fatty acids have a similar effect.]
• c) Gastrointestinal peptide hormones, intestinal peptides such as glucagon-like
peptide-1 and gastric inhibitory polypeptide ) increase sensitivity of beta cells to
glucose
• 2. Decreased secretion : synthesis and release of insulin are decreased during
starvation and stress
Mechanism of insulin secretion:
• • Penetration of glucose into beta cells, by Glut2 carriers, independently of the
presence of insulin.
• • Phosphorylation of glucose by glucokinase, then its metabolization with the
synthesis of ATP whose intracellular concentration increases.
• • This increase in ATP induces the closing of ATP-dependant potassium channels
and the cessation of potassium exit, with as a consequence depolarization and
opening of the voltage-dependant calcium channels. The entry of calcium causes
vesicles containing insulin to be exocytosed from the β cells.
Glucagon
• Glucagon is a peptide hormone secreted by the α cells of the pancreatic
islets of Langerhans.
• Glucagon acts to maintain blood glucose levels by activation of hepatic
glycogenolysis and gluconeogenesis.
• Glucagon is composed of 29 amino acids arranged in a single polypeptide
chain.
• Glucagon is synthesized as a large precursor molecule (preproglucagon)
• Pre-proglucagon is converted to glucagon through a series of proteolytic
cleavages.
• Like insulin, glucagon has a short half-life.
• Decrease blood glucose level stimulates secretion of glucagon and
epinephrine
• These hormones stimulate adenylate cyclase enzyme which converts ATP
into cyclic AMP
• Cyclic AMP stimulates protein kinase enzymes.
• Protein kinase enzyme stimulates phosphorylation of glycogen
phosphorylase , glycogen synthase, fructose 1,6 bisphosphatase, PFKI,
pyruvate kinase, pyruvate dehydrogenase, ACC
• As result glycogenesis, glycolysis and lipogenesis are shutdown and
glycogenolysis, GNG are stimulated.
Glucagon secretion
• Secretion is increased by:
➢Low blood glucose.
➢Catecholamines: Elevated levels of epinephrine and norepinephrine stimulate the release
of glucagon. Thus, during periods of physiologic stress, the elevated catecholamine levels
can override the effect on the α cell of circulating substrates. In these situations, regardless
of the concentration of blood glucose, glucagon levels are elevated in anticipation of
increased glucose use. In contrast, insulin levels are depressed
➢Amino acids, (for example, arginine) derived from a meal containing protein stimulate the
release of glucagon. The glucagon effectively prevents the hypoglycemia that would
otherwise occur as a result of the increased insulin secretion that also occurs after a protein
meal.
• Secretion Is decreased by:
➢Glucagon secretion is significantly decreased by elevated blood glucose and by insulin
➢Glucagon stimulates hepatic glycogenolysis and GNG