Endocrinology, Vol 111, 392-397, Copyright © 1982 by Endocrine Society

ARTICLES

The stimulus-secretion coupling of glucose-induced insulin release: effect of aminooxyacetate upon nutrient-stimulated insulin secretion

WJ Malaisse, F Malaisse-Lagae and A Sener

A possible role for the transfer of reducing equivalents between mitochondrial and cytoplasmic pools in the process of nutrient- stimulated insulin secretion was investigated by exposing rat pancreatic islets to aminooxyacetate, which inhibits transamination reactions and, hence, could impair the operation of the malate- aspartate shuttle. Aminooxyacetate (5.0 mM) decreased by 72-79% the transamination of exogenous pyruvate, L-leucine, or 2-ketoisocaproate but failed to affect the oxidation of glucose, L-leucine, or 2- ketoisocaproate and reduced by no more than 28-31% the oxidation of L- glutamine. In the 0.5-5.0 mM range, aminooxyacetate caused a dose- related inhibition of nutrient-stimulated insulin release, and lowered the cellular malate to pyruvate ratio. In the absence of both extracellular Ca2+ and exogenous nutrient, aminooxyacetate also inhibited the insulin release evoked by the combination of Ba2+ and theophylline. These findings suggest that a transfer of reducing equivalents to extramitochondrial sites participates in the process of insulin release, whether the latter involves the oxidation of exogenous or endogenous nutrients.

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