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.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology*; D005947:Glucose / Q000502:physiology; D005978:Glutathione / Q000032:analysis / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D000596:Amino Acids; D003510:Cyclohexanes; D003512:Cyclohexanones; D007328:Insulin; C028215:2-cyclohexen-1-one; D005978:Glutathione; D005947:Glucose; D002118:Calcium