The stimulus-secretion coupling of amino acid-induced insulin release: metabolism and cationic effects of leucine.
When isolated rat pancreatic islets are exposed to L-leucine (20 mM), the rate of NH4 production is close to the summed rates of L-[1-14C] leucine decarboxylation and alpha-ketoisocarproate production, whereas the rates of acetoacetate production and L-[U-14C]-leucine oxidation are compatible with conversion of each mole of the amino acid to one mole of acetoacetate and three moles of CO2. ATP content, ATP/ADP ratio, and adenylate charge are maintained at normal values by L-leucine, whereas the NADH/NAD+ ratio (but not the NADPH/NADP+ ratio) is significantly increased. The release of insulin evoked by L-leucine is potentiated by 2-ketoisovalerate, unaffected by L-valine, and inhibited by menadione. L-leucine mimicks the effect of D-glucose on 86Rb+ and 45Ca2+ handling by the islets. However, relative to its rate of oxidation, the insulinotropic effect of L-leucine is less marked than that of D-glucose. This may be due, in part at least, to a decrease in the oxidation of endogenous nutrients. It is concluded that the metabolic, cationic, and secretory effects of L-leucine in isolated islets are not incompatible with the fuel hypothesis for insulin release.
D000090:Acetoacetates / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002208:Caproates / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003641:Deamination; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D013268:Stimulation, Chemical
D000090:Acetoacetates; D002208:Caproates; D007328:Insulin; D002245:Carbon Dioxide; D000641:Ammonia; D007930:Leucine; D005947:Glucose; D012413:Rubidium; D002118:Calcium