Understanding mechanisms by which glibenclamide stimulates insulin release is important particularly given recent promising treatment by glibenclamide of permanent neonatal diabetic subjects. Anti-diabetic sulfonylureas are thought to stimulate insulin secretion solely by inhibiting their high affinity KATP channel receptors at the plasma membrane of β cells. This normally occurs during glucose...

The present study investigated the localization of ATP-sensitive K+ (KATP) channels in human skeletal muscle and the functional importance of these channels for human muscle K+ distribution at rest and during muscle activity. Membrane fractionation based on the giant vesicle technique or the sucrose-gradient technique in combination with Western blotting demonstrated that the KATP channels are ...

KATP channels are a newly defined class of potassium channels based on the physical association of an ABC protein, the sulfonylurea receptor, and a K+ inward rectifier subunit. The beta-cell KATP channel is composed of SUR1, the high-affinity sulfonylurea receptor with multiple TMDs and two NBFs, and KIR6.2, a weak inward rectifier, in a 1:1 stoichiometry. The pore of the channel is formed by K...

objective(s):this study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms. materials and methods: male wistar rats were anesthetized by thiopental sodium (50 mg/kg, ip) followed by iv injection of heparin (250 iu). remote ischemic preconditioning (ripc) was induce...

The effects of vasoconstrictor-receptor (neuropeptide Y, alpha-adrenergic, serotonergic, histaminergic) stimulation on currents through ATP-sensitive potassium (KATP) channels in arterial smooth muscle cells were examined. Whole-cell KATP currents, activated by the synthetic KATP channel opener pinacidil or by the endogenous vasodilator, calcitonin gene-related peptide, which acts through prote...

Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent s...

ATP-sensitive K channels (KATP channels) play an important role in glucose homeostasis. A single nucleotide polymorphism (SNP) in the Kir6.2 subunit causes a point mutation of Glu23 to lysine and reduces the ATP sensitivity of pancreatic KATP channels. The SNP found in 58% of Caucasians accounts for 15% of type 2 diabetes. Here we show evidence for dysregulations of muscular KATP channels with ...

Both protein kinase C (PKC) and adenosine receptor activation have been shown to enhance ATP-sensitive K+(KATP) channels. The present studies were designed to determine whether PKC mediates adenosine effects on the KATP channel. The dependence of KATP channel activity ( nP o) on intracellular ATP concentration ([ATP]i) was determined in excised rabbit ventricular membrane patches. External aden...

Insulin secretion from pancreatic β-cells is initiated by the closure of ATP-sensitive K+ channels (KATP) in response to high concentrations of glucose, and this action of glucose is counteracted by the hormone leptin, an adipokine that signals through the Ob-Rb receptor to increase KATP channel activity. Despite intensive investigations, the molecular basis for KATP channel regulation remains ...

Preconditioning has emerged as a valid strategy against different neurotoxic insults. Although the mechanisms underlying preconditioning are not fully understood, the activation of ATP-sensitive potassium (KATP) channels has been proposed to play a pivotal role in neuronal preconditioning. In the present work we examine whether minoxidil a KATP channel activator protects against the long-term t...