KCNJ11基因单核苷酸多态性与胰岛素分泌异常(英文)
作者单位：Department of cell biology and medical genetics.Health Science Center
会议名称：《中国的遗传学研究——遗传学进步推动中国西部经济与社会发...》
会议日期：2011年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
摘 要：The inwardly rectifying potassium channel,subfamily J,member 11(KCNJ11),with sulfonylurea receptor 1(SUR1),are the subunits of adenosine triphosphate(ATP)-sensitive K *** inward rectifier(Kir6.2) couples glucose metabolism to membrane excitability in pancreatic beta cells to control insulin *** single nucleotide polymorphisms(SNPs result in different *** of channel function because of mutations in KCNJ11,causes congenital hyperinsulinism(CHI),with its character is persistent insulin release despite severe *** are various affection on *** at arginine 301(to cysteine, glycine,histidine,or proline),reduced channel expression at the cell surface and caused rapid, spontaneous current *** mutations at R301A had equivalent surface expression with wide type(WT),it leaded to the inactivation gating *** near the Arg-301 residues caused subunit-subunit interface by destroying stabilizing channel *** contrast,gain of channel function because of mutations in Kir6.2,causes neonatal diabetes(ND),with its character is the decrease of insulin secretion despite *** can be classified as 1182V directly reducing ATP sensitivity and V59M,Q52R and I296L indirectly affecting ATP affinity. The latter group stabilizes the open conformation of Kir6.2 and functional uncouple SUR1 with *** results contribute to guiding the use of insulinotrpoic sulfonylurea(SU) *** addition,mutation of K23E has been associated with type 2 diabetes(T2D) as discovered by genome-wide association studies(GWAS).In summary,K channels play a key role in glucose-plasma insulin secretion in pancreatic beta *** review depicts types of SNPs of KCNJ11 gene and illustrates these associations with CHI,ND,and T2D.