KATP channel mutations in congenital hyperinsulinism

详细信息    查看全文

• 作者：C&#xe9 ; cile Saint-Martin PhD^a ; Jean-Baptiste Arnoux MD^b ; Pascale de Lonlay MD ; PhD^b ; Christine Bellann&#xe9 ; -Chantelot PharmD ; PhD^a ; ^{christine.bellanne-chantelot@psl.aphp.fr}
• 关键词：SUR1 ; Kir6.2 ; K_ATP channel ; Congenital hyperinsulinism ; Hyperinsulinemic hypoglycemia ; Diazoxide-responsiveness
• 刊名：Seminars in Pediatric Surgery
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：20
• 期：1
• 页码：18-22
• 全文大小：1113 K

文摘

Adenosine triphosphate (ATP)-sensitive potassium channels (K_ATP channels) have a central role in the regulation of insulin secretion in pancreatic β cells. They are octameric complexes organized around the central core constituted by the Kir6.2 subunits. The regulation of the channel itself takes place on the sulfonylurea receptor-1 subunit. The channel opens and closes according to the balance between adenine nucleotide ATP and adenosine diphosphate. Hyperinsulinemic hypoglycemia (also named congenital hyperinsulinism, or CHI) is associated with loss-of-function K_ATP channel mutations. Their frequency depends on the histopathological form and the responsiveness of CHI patients to diazoxide. ABCC8/KCNJ11 defects are identified in approximately 80 % of patients with CHI refractory to diazoxide. Within this group, focal forms are related to a paternally inherited KCNJ11 or ABCC8 mutation and the loss of the corresponding maternal allele in some pancreatic β cells leading to a focal lesion. Diffuse forms are mostly associated with recessively inherited mutations. Some patients with diffuse forms also carried a single K_ATP channel mutation. In contrast, K_ATP mutations are involved in 15 % of diazoxide-responsive CHI cases that are either sporadic or dominantly inherited.