Sulfonylureas (SU), commonly used in the treatment of type 2 diabetes mellitus (T2DM), stimulate insulin secretion by inhibiting adenosine triphosphate (ATP)-sensitive K(+) (KATP) channels in pancreatic β-cells. SU are now known to also activate cyclic adenosine monophosphate (cAMP) sensor Epac2 (cAMP-GEFII) to Rap1 signaling, which promotes insulin secretion. The different effects of various S...

ATP-regulated potassium (KATP) channel complexes of inward rectifier potassium channel (Kir) 6.2 and sulfonylurea receptor (SUR) 1 critically regulate pancreatic islet b-cell membrane potential, calcium influx, and insulin secretion, and consequently, represent important drug targets for metabolic disorders of glucose homeostasis. The KATP channel opener diazoxide is used clinically to treat in...

( ERPTransmural for glibenclamide ischemia 4.9 4 ms, P 0.019 versus control ischemia). Conclusions: KATP channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of KATP channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF. (...

Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been dem...

In smooth muscle cells, K(+) permeability is high, and this highly influences the resting membrane potential. Lymph propulsion is dependent on phasic contractions generated by smooth muscle cells of lymphatic vessels, and it is likely that K(+) channels play a critical role in regulating contractility in this tissue. The aim of this study was to investigate the contribution of distinct K(+) cha...

OBJECTIVES We investigated the effects of ischemic preconditioning (PC) on diabetic and failing human myocardium and the role of mitochondrial KATP channels on the response in these diseased tissues. BACKGROUND There is conflicting evidence to suggest that PC is a healthy heart phenomenon. METHODS Right atrial appendages were obtained from seven different groups of patients: nondiabetics, d...

The ATP-sensitive K+ (KATP) channel, composed of Kir6.2 and sulfonylurea receptor (SUR1), in pancreatic beta-cells is believed to serve as a metabolic sensor regulating insulin secretion according to glucose levels. Thus, genetic disruption of Kir6.2 expression may impair KATP channel function in glucose sensing and insulin secretion. Here we show evidence obtained from functional genetic assay...

The ATP-sensitive K channel (KATP channel) senses metabolic changes in the pancreatic -cell, thereby coupling metabolism to electrical activity and ultimately to insulin secretion. When KATP channels open, -cells hyperpolarize and insulin secretion is suppressed. The prediction that KATP channel “overactivity” should cause a diabetic state due to undersecretion of insulin has been dramatically ...

The ATP-sensitive K+-channel (KATP channel) plays a key role in insulin secretion from pancreatic beta cells. It is closed both by glucose metabolism and the sulfonylurea drugs that are used in the treatment of noninsulin-dependent diabetes mellitus, thereby initiating a membrane depolarization that activates voltage-dependent Ca2+ entry and insulin release. The beta cell KATP channel is a comp...

Glucagon, secreted from islet -cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of -cell secretory products zinc and insulin on isolated rat -cells, intact islets, and perfused pancreata. Islet glucagon secretion was ...