Potentiation of the insulin-releasing capacity of tolbutamide by thiols: studies on the isolated perfused pancreas.
It has been suggested that the islet thiol redox status plays a role in the regulation of beta-cell sensitivity in response to insulin secretagogues. Employing the isolated perfused rat pancreas, the effect of reduced glutathione (1 mM) and L-cysteine (5 mM) on insulin release induced by tolbutamide (0.2 mg/ml), glucose (5.6 and 11.1 mM) and tolbutamide (0.1 mg/ml) in the presence of 5.6 mM glucose was studied. In the absence of glucose or in the presence of 5.6 mM of glucose neither glutathione nor L-cysteine stimulated the release of insulin. Reduced glutathione potentiated the secretion induced by glucose (11.1 mM) during the first and the second phase. L-Cysteine potentiated only the first phase of glucose-induced insulin release, whereas the second phase was depressed. Both of the tested thiols potentiated the insulin secretory action of either tolbutamide (0.2 mg/ml) alone or tolbutamide (01. mg/ml) in the presence of glucose (5.6 mM). The data suggest that supplementation of thiols to the pancreatic beta-cells perse cannot initiate the insulin secretory process. It is also suggested that GSH and L-cysteine increase the sensitivity of beta-cells to the stimulatory action of tolbutamide and/or glucose.
D000818:Animals; D003545:Cysteine / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010084:Oxidation-Reduction; D010179:Pancreas / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology*
D007328:Insulin; D013438:Sulfhydryl Compounds; D014044:Tolbutamide; D005978:Glutathione; D003545:Cysteine