The whole-cell patch-clamp technique was used in adult mouse ventricular myocytes at 22 degrees C to study the transient outward current (I(to)) and its sensitivity to the antimycotics miconazole and clotrimazole, as well as to glybenclamide. I(to) elicited by depolarizing steps from a holding potential of -80 mV consisted of a fast inactivating component and a slowly inactivating component. In...

Several combination therapies have been tried for treating of type 2 diabetes to control more effectively fasting hyperglycemia and postprandial hyperglycemia. In this study, we have examined the effects of combining a novel, selective, and competitive dipeptidyl peptidase IV (DPP-IV) inhibitor, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate (E3024)...

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bil...

Background: Glybenclamide and metformin are two of the most common oral hypoglycemic drugs which are often used in treatment of type II diabetes mellitus. Toxicity due to these drugs may occur intentionally, accidentally, or even at the normal dosage because of the progression of such internal diseases as renal dysfunction. Methods: In this case series study, 59 patients poisoned with oral ...

background: glybenclamide and metformin are two of the most common oral hypoglycemic drugs which are often used in treatment of type ii diabetes mellitus. toxicity due to these drugs may occur intentionally, accidentally, or even at the normal dosage because of the progression of such internal diseases as renal dysfunction. methods: in this case series study, 59 patients poisoned with oral hypo...

OBJECTIVE-To determine whether alterations in counterregulatory responses to hypoglycemia through the modulation of ATP-sensitive K(+) channels (K(ATP) channels) in the ventromedial hypothalamus (VMH) are mediated by changes in GABAergic inhibitory tone in the VMH, we examined whether opening and closing K(ATP) channels in the VMH alter local GABA levels and whether the effects of modulating K(...

Denatonium, one of the most bitter-tasting substances known, stimulated insulin secretion in clonal HIT-T15 beta-cells and rat pancreatic islets. Stimulation of release began promptly after exposure of the beta-cells to denatonium, reached peak rates after 4-5 min, and then declined to near basal values after 20-30 min. In islets, no effect was observed at 2.8 mmol/;l glucose, whereas a marked ...

The effect of several hypoglycemic sulphonylureas upon the oxidative phosphorylation of intact rat liver mitochondria was examined. Following results were obtained and discussed in relation to hypoglycemic action and uncoupling site of these drugs. 1. All hypoglycemic sulphonylurea drugs tested, i.e., tolbutamide, carbutamide, chlorpropamide, acetohexamide, glybenclamide, and glyclopyramide wer...