Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels

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Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels.

ATP-sensitive potassium (KATP) channels couple the metabolic status of a cell to its membrane potential-a property that endows pancreatic beta-cells with the ability to regulate insulin secretion in accordance with changes in blood glucose. The channel comprises four subunits each of Kir6.2 and the sulphonylurea receptor (SUR1). Here, we report that KATP channels undergo rapid internalisation f...

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Anti-nociceptive effect of cimetidine in mice: the role of ATP-sensitive potassium channels

Recent studies have shown that intracerebroventricular administration of cimetidine (CIM) induces anti-nociceptive and anti–inflammatory effects in rats. However, the underlying mechanism of CIM effect has not been determined yet. This study was planned to determine the anti-nociceptive effect of CIM (50 mg/kg, i.p.) in male mice (25-30 g, n = 80) using tail flick test. Also, the role of ATP-se...

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Cardiovascular ATP-sensitive potassium channels

Sulfonylurea drugs stimulate endogenous insulin secretion by blockade of ATP-sensitive potassium channels in pancreatic beta cells. These drugs are widely used in the treatment of type 2 diabetes. However, as ATP-sensitive potassium channels also exist in cardiomyocytes and coronary and peripheral arterial vascular smooth muscle cells, sulfonylurea drug usage in theory may cause unwanted cardio...

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The molecular mechanisms and pharmacotherapy of ATP-sensitive potassium channel gene mutations underlying neonatal diabetes

Neonatal diabetes mellitus (NDM) is a monogenic disorder caused by mutations in genes involved in regulation of insulin secretion from pancreatic β-cells. Mutations in the KCNJ11 and ABCC8 genes, encoding the adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel Kir6.2 and SUR1 subunits, respectively, are found in ∼50% of NDM patients. In the pancreatic β-cell, K(ATP) channel activi...

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Anti-nociceptive effect of cimetidine in mice: the role of ATP-sensitive potassium channels

Recent studies have shown that intracerebroventricular administration of cimetidine (CIM) induces anti-nociceptive and anti–inflammatory effects in rats. However, the underlying mechanism of CIM effect has not been determined yet. This study was planned to determine the anti-nociceptive effect of CIM (50 mg/kg, i.p.) in male mice (25-30 g, n = 80) using tail flick test. Also, the role of ATP-se...

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ژورنال

عنوان ژورنال: The EMBO Journal

سال: 2006

ISSN: 0261-4189,1460-2075

DOI: 10.1038/sj.emboj.7601275