title: The characterization of phenazine methosulfate stimulated insulin secretion.
abstract: This investigation was initiated to characterize the stimulation of insulin secretion by phenazine methosulfate (PMS). Islets of Langerhans, isolated by the collagenase method from normal rats and rats pre-injected with either streptozotocin or 6-aminonicotinamide, were exposed to PMS under various experimental conditions and insulin secretion in response to PMS, glucose and pyridine nucleotides was determined. Insulin releasing action of PMS was dose-, time- and temperature-related, occurred in the absence of glucose, and was inhibited by epinephrine, but not by mannoheptulose. In the perifusion system, the pattern of response induced by PMS was spike-like release reaching a maximum in 5 min and declining rapidly to half-maximal value in 10 min. After exposure of islets to beta-cytotoxin either in vivo or in vitro, complete reversal of the cytotoxic effect was obtained with PMS which induced release of insulin in both normal and beta-cytotoxin islets pre-treated. It is concluded that islets depleted of coenzymes could still secrete insulin in response to a reactive proton donor, which might act by substituting for coenzymes and that the immediate action of beta-cytotoxins does not completely arrest the secretory mechanisms in islets of Langerhans.
mesh_terms: D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008356:Mannoheptulose / Q000494:pharmacology; D008773:Methylphenazonium Methosulfate / Q000494:pharmacology*; D010619:Phenazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology; D013696:Temperature; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D007328:Insulin; D010619:Phenazines; D011725:Pyridines; D008773:Methylphenazonium Methosulfate; D013311:Streptozocin; D008356:Mannoheptulose; D000496:Alloxan; D014044:Tolbutamide; D005947:Glucose; D004837:Epinephrine