The coupling of metabolic to secretory events in pancreatic islets: effects of 2-cyclohexene-1-one upon GSH content and secretory behaviour.

The GSH content and GSH/GSSG ratio were decreased in rat pancreatic islets exposed to 2-cyclohexene-1-one (CHX; 1.0 mM), but the drug failed to affect the cytosolic NADH/NAD+ and NADPH/NADP+ ratios. This coincided with inhibition of D-glucose oxidation, whilst the oxidation of L-leucine and L-glutamine was little affected by CHX (1.0 mM). The release of insulin evoked by either D-glucose or 2-ketoisocaproate was inhibited by CHX (1.0 mM), whereas such was not the case for insulin secretion induced by L-leucine, alone or in combination with L-glutamine. The latter amino acid protected the B-cell against the inhibitory action of CHX upon glucose-stimulated insulin release. CHX severely altered the normal relationship between nutrient oxidation, [45Ca] net uptake and insulin release. Since CHX also inhibited insulin release evoked by non-nutrient secretagogues, it is speculated that GSH may be involved in several cytophysiological processes including the control of glycolysis, intracellular calcium distribution, and responsiveness to this cation of Ca2+-sensitive targets.