Stimulation of pancreatic islet metabolism and insulin release by a nonmetabolizable amino acid

Abstract

The leucine analog beta-2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH) activates glutamate dehydrogenase [L-glutamate:NAD+ oxidoreductase (deaminating), EC 1.4.1.2] in pancreatic islet homogenates. In intact islets, BCH increased the islet content or output of NH4+, 2-ketoglutarate, malate, pyruvate, and alanine. BCH caused a dose-related increase in 14CO2 output from islets prelabeled with L-[U-14C]glutamine. BCH increased the islet content of ATP and stimulated both 45Ca net uptake and insulin release. The capacity of seven distinct amino acids to activate glutamate dehydrogenase tightly correlated with their ability to augment 14CO2 output from islets prelabeled with [U-14C]-glutamine and to stimulate insulin release in the presence of L-glutamine. The activation of glutamate dehydrogenase by BCH may thus account for the insulin-releasing capacity of the leucine analog.