期刊
DIABETES OBESITY & METABOLISM
卷 14, 期 -, 页码 136-142出版社
WILEY
DOI: 10.1111/j.1463-1326.2012.01649.x
关键词
beta-cell; Bax; Bcl-2; calcium; Ca2+; diabetes; ER stress; Na; Ca exchange; NCX; plasma membrane Ca2+-ATPase; PMCA; sodium-calcium exchange
资金
- Belgian Fund for Scientific Research [FRSM 3.4593.04, 3.4527.08]
- EFSD/Novo Nordisk Programme in Diabetes Research [2005/6]
Ca2+ extrusion from the beta-cell is mediated by two processes the Na/Ca exchanger (NCX) and the plasma membrane Ca2+-ATPase (PMCA). Gain of function studies show that overexpression of NCX or PMCA leads to endoplasmic reticulum (ER) Ca2+ depletion with subsequent ER stress, decrease in beta-cell proliferation and beta-cell death by apoptosis. Interestingly, chronic exposure to cytokines or high free fatty acid concentrations also induce ER Ca2+ depletion and beta-cell death in diabetes. Loss of function studies show, on the contrary, that heterozygous inactivation of NCX1 (Ncx1+/-) leads to an increase in beta-cell function (insulin production and release), and a fivefold increase in both beta-cell mass and proliferation. The mutation also increases beta-cell resistance to hypoxia, and Ncx1+/- islets show a two to four times higher rate of diabetes cure than Ncx1+/+ islets when transplanted in diabetic animals. Thus, down-regulation of the Na/Ca exchanger leads to various changes in beta-cell function that are opposite to the major abnormalities seen in diabetes. This provides a unique model for the prevention and treatment of beta-cell dysfunction in diabetes and following islet transplantation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据