The stimulus-secretion coupling of glucose-induced insulin release: effect of aminooxyacetate upon nutrient-stimulated insulin secretion.
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.
D000085:Acetates / Q000494:pharmacology*; D000625:Aminooxyacetic Acid / Q000494:pharmacology*; D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D008293:Malates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats
D000085:Acetates; D007328:Insulin; D007651:Keto Acids; D008293:Malates; D011773:Pyruvates; D005973:Glutamine; D000625:Aminooxyacetic Acid; C013082:alpha-ketoisocaproic acid; C030298:malic acid; D019289:Pyruvic Acid; D007930:Leucine; D005947:Glucose