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...

Mutations to the ATP-sensitive K(+) channel (KATP channel) that reduce the sensitivity of ATP inhibition cause neonatal diabetes mellitus via suppression of β-cell glucose-stimulated free calcium activity ([Ca(2+)]i) and insulin secretion. Connexin-36 (Cx36) gap junctions also regulate islet electrical activity; upon knockout of Cx36, β-cells show [Ca(2+)]i elevations at basal glucose. We hypot...

In the present study, we have investigated the mechanism underlying the activation by 5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3- pyridinecarboxamidine (KRN4884), a new K+ channel opener, of ATP-sensitive K+ (KATP) channels in single ventricular cells of guinea pig hearts by the inside-out patch-clamp method. In the presence of intracellular ATP (1 mM), KRN4884 (0.1-3 microM) activated KATP...

ATP-sensitive potassium (KATP) channels link cell metabolism to membrane excitability and are involved in a wide range of physiological processes including hormone secretion, control of vascular tone, and protection of cardiac and neuronal cells against ischemic injuries. In pancreatic β-cells, KATP channels play a key role in glucose-stimulated insulin secretion, and gain or loss of channel fu...

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 ...

Ghrelin, a hunger signalling peptide derived from the peripheral tissues, overcomes the satiety signals evoked by anorexigenic molecules, such as cholecystokinin (CCK) and leptin, to stimulate feeding. Using in vivo and in vitro electrophysiological techniques, we show that ghrelin hyperpolarizes neurons and inhibits currents evoked by leptin and CCK-8. Administering a KATP channel antagonist o...

ATP-sensitive K+ (KATP) channels are present in a wide variety of tissues. The sensitivity of these channels to closure by cytosolic ATP (ATPi) varies significantly among different tissues and even within the same tissue. The purpose of this study was to test the hypothesis that negative surface charges modulate the sensitivity of the KATP channels to ATPi by influencing surface potential in th...

Objective: The aim was to improve the measurement of both the time course and amplitude of anoxia-induced K -channel current ATP 1 (I ) in isolated heart cells to specify the role of these channels in the time course of K accumulation in the ischemic myocardium. KATP Methods: Ionic currents in isolated ventricular heart cells of the mouse were measured with a patch clamp technique under normoxi...

Existing concepts and models for glucose-stimulated insulin secretion (GSIS) are overviewed and a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model has been created on the basis of in vitro data on application of a square wave high glucose in the absence of any other stimulatory inputs. Glucose elicits rapid insulin release through an ade...

BACKGROUND AND PURPOSE The 2-propyl-1,4 benzoxazine (AM10) shows a peculiar behaviour in skeletal muscle, inhibiting or opening the ATP-sensitive K(+) (KATP) channel in the absence and presence of ATP, respectively. We focused on tissue selectivity and mechanism of action of AM10 by testing its effects on pancreatic KATP channels by means of both in vitro and in vivo investigations. EXPERIMEN...