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In the field of molecular biology, the sulfonylurea receptors (SUR) are membrane proteins which are the molecular targets of the sulfonylurea class of antidiabetic drugs whose mechanism of action is to promote insulin release from pancreatic beta cells. More specifically, SUR proteins are subunits of the inward-rectifier potassium ion channels K_ir6.x.^[1] The association of four K_ir6.x and four SUR subunits form an ion conducting channel commonly referred to as the K_ATP channel.

There are three forms of the sulfonylurea receptor, SUR1encoded by the ABCC8 gene and SUR2A and SUR2B which are splice variants arising from a single ABCC9 gene.^[2]

Function

The primary function of the sulfonylurea receptor is to sense intracellular levels of the nucleotides ATP and ADP and in response facilitate the open or closing its associated K_ir6.x potassium channel. Hence the K_ATP channel monitors the energy balance within the cell.^[3]

Depending on the tissue in which the K_ATP channel is expressed, altering the membrane potential can trigger a variety of down stream events. For example, in pancreatic beta cells, high levels of glucose lead to increased production of ATP which in turn binds to the K_ATP channel resulting in channel closure. The reduction in membrane potential in turn opens voltage-dependent calcium channels increasing intracellular calcium concentrations which triggers exocytosis of insulin.

Tissue distribution

The isoforms of the sulfonylurea receptor have the following tissue distribution:

• adipose tissue - SUR2B/K_ir6.1
• pancreatic beta cells - SUR1/K_ir6.2
• cardiac myocytes - SUR2A
• skeletal muscle - SUR2A
• smooth muscle - SUB2B

Disease linkage

The SUR1 protein is coded by the ABCC8 gene and is associated with congenital hyperinsulinism^[4] and susceptibility to type 2 diabetes.^[5]

References

1. ^ Campbell JD, Sansom MS, Ashcroft FM (2003). "Potassium channel regulation". EMBO Rep 4 (11): 1038–42. doi:10.1038/sj.embor.7400003. PMID 14593442. 
2. ^ Aguilar-Bryan L, Clement JP 4th, Gonzalez G, Kunjilwar K, Babenko A, Bryan J (1998). "Toward understanding the assembly and structure of KATP channels". Physiol Rev 78 (1): 227–45. PMID 9457174. 
3. ^ Nichols CG (2006). "KATP channels as molecular sensors of cellular metabolism". Nature 440 (7083): 470–6. doi:10.1038/nature04711. PMID 16554807. 
4. ^ Fournet JC, Junien C (2004). "Genetics of congenital hyperinsulinism". Endocr Pathol 15 (3): 233–40. doi:10.1385/EP:15:3:233. PMID 15640549. 
5. ^ Reis AF, Velho G (2002). "Sulfonylurea receptor -1 (SUR1): genetic and metabolic evidences for a role in the susceptibility to type 2 diabetes mellitus". Diabetes Metab 28 (1): 14–9. PMID 11938023. 

External links

• MeSH sulfonylurea+receptor

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