Carbon dioxide is an important regulator of vascular tone. Glibenclamide, an inhibitor of ATP-sensitive potassium channel (K(ATP)) activation, significantly blunts vasodilation in response to hypercapnic acidosis in animals. We investigated whether glibenclamide also alters the cerebral and ocular vasodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a control...

BACKGROUND The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular smooth muscle K+ATP channels in regulating coronary blood flow under resting conditions, during increments in myocardial metabolic demand produced by treadmill exercise, and in response to a brief ischemic stimulus. METHODS AND RESULTS Ten chronically instru...

OBJECTIVE To compare the effects of repaglinide, glipizide, and glibenclamide on insulin secretion and postprandial glucose after a single standard 500-kcal test meal. RESEARCH DESIGN AND METHODS A total of 12 type 2 diabetic patients with early diabetes (mean HbA(1c) of 6.1%) and 12 matched control subjects were enrolled in this randomized, double-blind, crossover trial. Subjects received pl...

ATP-dependent K(+) channels are composed of pore-forming subunits of the Kir6.x family and of sulfonylurea receptors (SURs). SUR1, expressed in pancreatic beta-cells, has a higher affinity for sulfonylureas, such as glibenclamide, than SUR2B, expressed in smooth muscle. This difference is mainly caused by serine 1237 in SUR1 corresponding to tyrosine 1206 in SUR2B. To increase the affinity of S...

We developed a step-by-step experimental protocol using differential scanning calorimetry (DSC), dynamic vapour sorption (DVS), polarized light microscopy (PLM) and a small-scale dissolution apparatus (μDISS Profiler) to investigate the mechanism (solid-to-solid or solution-mediated) by which crystallization of amorphous drugs occurs upon dissolution. This protocol then guided how to stabilize ...

A ctivating mutations in the KCNJ11 gene, which code for the ATPsensitive K channel subunit Kir6.2, are the most common cause of permanent neonatal diabetes. Recently, a switch from insulin treatment to oral sulfonylurea has been proposed if genetic testing reveals sulfonylurea-sensitive KCNJ11 mutations (1). Until now, hurdles for early treatment were 1) the time until the mutation analysis is...

We examined the effect of endothelium and lipid emulsion on vasodilation induced by minoxidil at a toxic dose determined underlying mechanism. The effects endothelial denudation, NW-nitro-L-arginine methyl ester (L-NAME), methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), glibenclamide, alone or in combination, minoxidil-induced endothelium-intact rat aorta were examined. Addit...