ABCC8 antibody

Background of ABCC8 antibody

The relation ship between glucose metabolism and insulin secretion from the pancreatic beta cells is linked with ATP-sensitive potassium channels (KATP). IN response to glucose metabolism, the ATP-sensitive potassium channels are inactivated due to an increase in ATP/ADP ratio, resulting in membrane depolarization and calcium influx through voltage dependent L-type Ca+2 channels. The KATPs are composed 4 units of inwardly rectifying K channel subunit (Kir6.2) and 4 copies of regulatory subunit SUR1 in an octameric complex. SUR 1 is a member of ATP binding cassette super family. SUR receptor confers the sensitivity of Kir6.2 to ATP/ADP sensitivity and to pharmacological agents such as sulfonylurea and diazoxide that close or open the KATP channels. The persistent heyperinsulinimic hypoglycemia in infancy (PHHI) is familial disorder due to defect in negative feed back in response to low glucose levels. SUR1 was mapped on chromosome 11p14-15.1, the same location where the gene for PHHI is located (1). It has been shown that the expression of Kir6.2 and SUR1 are regulated by glucose levels and the actives of glucogon-like peptide receptor1 (2). Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene.

SUR1 is a 1581 amino acid protein with an ATP binding domain with two nucleotide-binding folds (NBFs) and binding sites for sulfonylureas, like glibenclamide, and for channel openers. SUR contains three hydrophobic domains, TM(0), TM(1), and TM(2), with nucleotide binding folds following TM(1) and TM(2). The protein is glycosylated at position 10 on Asn. The SUR1 gene is expressed in at least 4 multiple splice variants ere are multiple splice variants, these splice variants originate from the splicing of the coding region of NFB and lack of axon 17 (SUR1Delta17), axon 19 (SUR1Delta 19) and both (SUR1Delta 17/19) and the fourth is a COOH terminal fragment formed by Exxon 31-39 containing the last 2 TMD and the COOH terminal (SUR1C). The various splice variants of SUR1 are expressed in various tissues with strong expression of SUR1C in cardiomyocytes (3). Only SUR1 and SUR1Delta 17 exhibit high affinity binding sites for sulfonylurea and other pharmacological agents. Several point mutations in the NFB region of SUR1 are also described in NIDDM. A total of five amino acid substitutions and 17 silent mutations were noted by examining all 39 axons of this gene in NIDDM patients form Japan. Two rare novel mutations, D811N in axon 20 and R835C in axon 21, were identified in the first nucleotide-binding fold (NBF), a functionally important region of SUR1, in one patient each, both heterozygotes.