{"id":"1511","type":{"id":"29","name":"Biochemical Pathways","urlId":"biochemical-pathway","subtypes":[],"schema":"http:\/\/schema.org\/Article","numTerms":0},"subtype":{"id":"81","name":"Hormones \u0026 Cell Signaling","urlId":"hormones-cell-signaling"},"urlId":"insulin","role":"term","course":{"id":"6","urlId":"biochemistry","name":"Biochemistry"},"children":[],"name":"Insulin","demo":0,"description":"INSULIN\n* [Peptide](\/term\/biochemistry\/peptide-bonds) hormone secreted by pancreatic beta cells\n* Promotes anabolic (synthetic pathways): energy requiring\n* Binds receptor tyrosine kinases (liver, muscle, adipose tissue, etc.)\n\n[PANCREAS](\/term\/biochemistry\/pancreas)\n## [Islets of Langerhans](\/term\/biochemistry\/islets-of-langerhans) (1-2% of pancreatic beta cells)\n* Beta cell: secretes insulin\n* Alpha cell: secretes [glucagon](\/term\/biochemistry\/glucagon-mechanism-of-action) (opposes insulin)\n\nINSULIN SYNTHESIS AND STRUCTURE\n## Components of insulin\n* N-terminal signal peptide: targets preproinsulin to endoplasmic reticulum\n* B chain: portion of final hormone\n* C peptide: marker of endogenously synthesized insulin\n* A chain: portion of final hormone\n* Two [disulfide bonds](\/term\/biochemistry\/disulfide): 1 within A chain, another between B and A chains\n## Synthesis\n* Signal peptide cleaved from preproinsulin in ER of beta cells to form proinsulin\n* C peptide cleaved from proinsulin in Golgi apparatus\n* Two products: C peptide and insulin\n## C peptide\n* Longer half-life than insulin: marker of insulin synthesis and secretion\n## Insulin\n* Half-life ~ 6 min.\n\nINSULIN SECRETION\n## Pancreatic beta cell surface\n* Voltage-dependent Ca2+ [channel](\/term\/cell-biology\/passive-transport) (closed)\n* ATP-sensitive K+ channel (open): K+ flows down concentration gradient out of cell\n* GLUT2: tissue-specific glucose transporter (beta cells and liver cells)\n## Steps of secretion\n1.\tEat carbohydrate rich meal: plasma glucose is high\n2.\tGlucose enters beta cell via GLUT2\n3.\t[Glucokinase](\/term\/biochemistry\/glucokinase) phosphorylates\/sequesters glucose in cell (glucose --\u003E glucose 6P)\n* Glucokinase: tissue specific (beta cells and liver cells), high Km and high Vmax\n4.\t[Glycolysis](\/term\/biochemistry\/glycolysis): Glucose 6P --\u003E ATP \n5.\tATP binds K+ channel and closes it: depolarizes membrane \u0026 activates Ca2+ channel\n6.\tCa2+ influx promotes exocytosis and release of insulin secretory granules\n\n## Pancreatic beta cells: most important glucose-sensing cells\n* GLUT2:  high Km, only bind glucose when plasma glucose is high\n* Glucokinase: High Km, high Vmax \u0026 no product inhibition (can continue trapping glucose even when intracellular glucose concen. rise)\n\nINSULIN MECHANISM OF ACTION\n## Key insulin-sensitive tissues: liver, muscle \u0026 adipose tissue\n1.\tInsulin binds receptor tyrosine kinase: activates intracellular RTK beta subunits\n2.\tAutophosphorylation: activated RTK phosphorylates other intracellular proteins\n3.\tInitiates signaling cascade\n4.\tMuscle \u0026 adipose: signaling cascade mobilizes GLUT4 transporters from intracellular storage to cell surface\n* Increases glucose absorption\n* Seconds after insulin binding\n* Does not occur in hepatocytes\n5. Activates anabolic enzymes: glycogen, protein and lipid synthesis (~minutes\/hours)\n* Promotes glucose storage when glucose is abundant\n6. Inhibits catabolic enzymes: glycogen \u0026 lipid breakdown (~minutes\/hours)\n7. Inhibits [gluconeogenesis](\/term\/biochemistry\/gluconeogenesis)(~minutes\/hours)\n8. 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