The stimulus-secretion coupling of glucose-induced insulin release. Thiol: disulfide balance in pancreatic islets.
An increase in the production rate of reduced pyridine nucleotides is currently considered as a coupling factor between metabolic and distal events in the process of glucose-stimulated insulin release. The possible participation in such a coupling of thiol: disulfide interchanges was investigated in rat pancreatic islets. NADPH-dependent glutathione reductase and glutathione-cystine transhydrogenase activities were present in islet homogenates, whereas no glutathione peroxidase activity could be detected. In intact islets, glucose (16.7 mM) augmented both the GSH/GSSG ratio (from a basal value of 6.7 +/- 0.6 to 8.4 +/- 0.4) and the tissue content of sulphydryl groups (from a basal value of 119 +/- 7 to 170 +/- 9 pmol/microgram protein). The latter effect was mimicked by D-glyceraldehyde, 2-ketoisocaproate, anoxia and KCN; it failed to be reproduced by L-glucose or D-fructose, was unaffected by theophylline, and was inhibited by D-mannoheptulose, iodoacetate, menadione, cytochalasin B and the absence of extracellular Ca2+. These findings support the view that a glucose-induced reduction of disulphide bridges to sulphydryl groups participates in the stimulus-secretion coupling of nutrient-induced insulin release.
D000818:Animals; D003553:Cystine / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014018:Tissue Distribution
D007328:Insulin; D013438:Sulfhydryl Compounds; D003553:Cystine; D009249:NADP; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; C020665:glutathione-cystine transhydrogenase; D005978:Glutathione; D005947:Glucose; D019803:Glutathione Disulfide