Interaction of branched chain amino acids and keto acids upon pancreatic islet metabolism and insulin secretion.
Insulin release evoked by 2-ketoisocaproate from isolated rat pancreatic islets was inhibited by L-valine, L-isoleucine, L-norvaline, and L-norleucine. The stereo-specificity of the inhibition and the finding that the decrease in secretory rate was correlated to the capacity of these amino acids to undergo transamination with the keto acid secretagogue suggested that a branched chain amino acid aminotransferase enzyme was the site of interaction of these substrates. The stimulation of transamination by these amino acids was accompanied by a decrease in the primary decarboxylation and oxidation of 2-ketoisocaproate in the tissue and a reduction in islet acetoacetate production. The oxidation of the amino acid substrate was slightly increased in the presence of 2-ketoisocaproate. Nevertheless, the oxidation rate of exogenous substrates and respiration were higher in the presence of 2-ketoisocaproate than when this substrate was combined with an amino acid. The action of 2-ketoisocaproate to increase the ratios of NADH/NAD+ and NADPH/NADP+, to enhance the uptake of 45Ca by islet tissue, and to promote proinsulin biosynthesis was also suppressed by the addition of branched chain amino acids to the incubation media. Radioisotopic uptake measurements suggested that many of these observations could be related to changes in the intracellular concentration of 2-ketoisocaproate in islet tissue.
D000597:Amino Acids, Branched-Chain / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D005260:Female; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000378:metabolism / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D013329:Structure-Activity Relationship
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D007651:Keto Acids; D009243:NAD; D009249:NADP; C013082:alpha-ketoisocaproic acid; D002118:Calcium