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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