Sulfonylurea receptors

Sulfonylurea receptor 1 (SUR1) Sulfonylurea (tolbutamide) Decreased tolbutamide-stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene (94) Susceptibility to type II diabetes (95)... 

The sulfonylurea receptor was identified as an adenosine triphosphate (ATP) sensitive potassium (Katp) channel that is present on the (3-cell membrane surface. Closure of these K tp channels causes (3-cell membrane... 

These drugs stimulate insulin secretion from pancreatic P-cells (so called sulfonylurea receptors ) which cause depolarisation by reducing conductance of... 

Sulfonylureas bind to a 140-kDa high-affinity sulfonylurea receptor (Figure 41-2) that is associated with a beta-cell inward rectifier ATP-sensitive potassium channel. Binding of a sulfonylurea inhibits the efflux of potassium ions through the channel and results in depolarization. Depolarization opens a voltage-gated calcium channel and results in calcium influx and the release of preformed insulin. 

NIDDM is strongly associated with obesity,dd and dieting and exercise often provide adequate control of blood glucose. Sulfonylurea drugs such as the following induce an increase in the number of insulin receptors formed and are also widely used in treatment of the condition.66 These drugs bind to and inhibit ATP-sensitive K+ channels in the P cell membranes. A defect in this sulfonylurea receptor has been associated with excessive insulin secretion... 

The meglitinides bind with high affinity to a site, distinct from the sulfonylurea receptor site, on the ATP-sensitive potassium channels in pancreatic beta cells and stimulate insulin secretion. After binding, the ATP-dependent potassium channels are closed, reducing potassium efflux and depolarizing the cell membrane. The meglitinides do not have to be internalized in the membrane, in contrast to the sulfonylureas. This may explain their rapid onset of... 

New data on the sulfonylurea receptor as part of the ATP-dependent potassium channel (SUR-1 in the beta pancreatic cells, involved in insulin secretion, and SUR-2 in the myocardium, involved in cardiac adaptation during ischemia) has still not yielded a definitive answer. The available experimental and clinical data have been systematically reviewed (29). The conclusion was that experimentally the effects of sulfonylureas on heart muscle are both deleterious and protective for glibenclamide while tolbutamide, glimepiride, and gliclazide have no effects. There seem to be no adverse cardiac consequences of chronic treatment with sulfonylureas. 

Bryan J, Crane A, Vila-Carriles WH, et al. Insulin sec-retagogues, sulfonylurea receptors and K(ATP) channels. Curr Pharm Des. 2005 11 2699-2716. 

Insulin secretagogues bind to sulfonylurea receptors in potassium channels in extrapancreatic tissues but the binding affinity varies among the drug classes and is much less avid than for the B cell receptors. The clinical significance of extrapancreatic binding is not known. 

Sulfonylurea receptor cloned, associated with hyperinsulin secretion maps to chromosome 1 lpl5.1 38... 

The ion channel/transporter group is represented by several receptors associated with the long QT syndrome, and the sulfonylurea receptor that is... 

Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, Aguilar-Bryan L, Gagel RF, Bryan J. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995 268(5209) 426-429. 

Thomas PM, Wohllk N, Huang E, Kuhnle U, Rabl W, Gagel RF, Cote GJ. Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet 1996 59(3) 510-518. 

Abo-Elghar, G. E., Fujiyoshi, P., and Matsumura, F., Significance of the sulfonylurea receptor (SUR) as the target of diflubenzuron in chitin synthesis inhibition in Drosophila melanogaster and Blat-tella gertnanica, Insect Biochem. Molec. Biol., 34, 743, 2004. 

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