Anesthesia Pharmacology: Diabetes
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Insulin is a small protein,composed of two chains, A and B.
Pancreatic B cells produced proinsulin, the insulin precursor, which consists of a single-chain protein
Proinsulin, following Golgi apparatus processing, is packaged into granules where proteases proinsulin is hydrolyzed to insulin and C-peptide
Pancreatic B cell granules store insulin in crystals, 2 atoms of zinc six molecules of insulin.
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Normally low basal rate from pancreatic B cells
Higher stimulated rate in response to:
Glucose
Other sugars (e.g. mannose)
Certain amino acids (e.g. leucine, arginine)
Vagal nerve activity
Hyperglycemia
Increased intracellular ATP concentration
Higher intracellular ATP closes ATP-dependent potassium channels
Decreased outward potassium current causes pancreatic B cell depolarization and opens voltage-gated calcium channels
Increased intracellular calcium promotes insulin secretion
Intracellular second messengers modulate release:
Cyclic AMP
Inositol triphosphate
Diacylglycerol
Circulating insulin is removed by: liver and kidney
Liver: clears 60% of insulin released from the pancreas
Kidney: clears about 35-40% of endogenous insulin (in insulin-treated diabetics -- subcutaneous injections -- the kidney may clear as much as 60%.)
Catabolism
Cleavage of sulfide linkage between A and B chains space for (catalyzed by glutathione insulin transhydrogenase and (insulinase)than
Further degradation: proteolysis
Karam, J. H., Pancreatic Hormones and Antidiabetic Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 684-703
Foster, D. W., Diabetes Mellitus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2060-2080
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