Signal function of metabolism of neutral amino acids and 2-keto acids for initiation of insulin secretion.

2-Ketocaproate and 2-ketoisocaproate were equally potent insulin secretagogues. The insulin secretory potency of L-leucine was less than half of that of the keto acids and L-norleucine did not induce any insulin release by isolated islets and by the perfused pancreas from ob/ob mice. Rates of decarboxylation of 2-keto-[1-14C]isocaproate and of 2-keto-[1-14C]caproate were equally high. The finding is consistent with the view that enhanced production of reducing equivalents is necessary for initiation of insulin release. The rates of decarboxylation and transamination of L-[1-14C]leucine by isolated pancreatic islets were several times higher than the rates observed with L-[1-14C]norleucine. Thus, the high activity of the pancreatic islet branched-chain amino acid aminotransferase may be important for the recognition of L-leucine as an insulin secretagogue by pancreatic B-cells.