Thiol-dependent and non-thiol-dependent stimulations of insulin release.
The effects of reduced glutathione (GSH) and diamide (an oxidant of GSH) on insulin release induced by glucose, glyceraldehyde, leucine, tolbutamide, glibenclamide, Ca-ionophore A-23187, isoprenaline, and dbcAMP were studied using isolated rat pancreatic islets. In the absence or presence of low glucose (5.6 mM) neither GSH (0.1 mM) nor diamide (0.1 mM) affected insulin release. Insulinotropic action of glucose (11.1 mM) and glyceraldehyde (11.1 mM), and that of tolbutamide (0.1 mg/ml) and leucine (10 mM) both in the presence of 11.1 mM glucose was further augmented by GSH and inhibited by diamide. GSH (0.05-1 mM) and diamide (0.1 mM) failed to affect the insulin secretion evoked by glibenclamide (5 micrograms/ml) + glucose (11.1 mM), Ca-ionophore A-23187 (50 micrograms/ml) + glucose (5.6 mM), isoprenaline (1 microM) + glucose (5.6 mM), and db-cAMP (1 mM) + glucose (5.6 mM). The data suggest that the insulin-releasing capacity of glucose, glyceraldehyde, tolbutamide, and leucine depends on the redox state of islet thiols, whereas the insulin-releasing effect of glibenclamide, Ca-ionophore, isoprenaline, and db-cAMP does not. The possibility that thiol dependency is associated with those compounds increasing Ca uptake but not with compounds acting as Ca-ionophores or only by increasing intracellular cAMP is discussed.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D014044:Tolbutamide / Q000494:pharmacology
D007328:Insulin; D013438:Sulfhydryl Compounds; D003958:Diamide; D005985:Glyceraldehyde; D000001:Calcimycin; D003994:Bucladesine; D014044:Tolbutamide; D005978:Glutathione; D007930:Leucine; D005947:Glucose; D007545:Isoproterenol; D005905:Glyburide; D002118:Calcium