The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes
The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes
复制标题
DOI：
10.2337/diabetes.54.3.657
复制
发表时间：
2005-03-01
期刊：
影响因子：
7.7
通讯作者：
Ogawa, S
中科院分区：
文献类型：
--
作者：
Ozawa, K;Miyazaki, M;Ogawa, S
为了确定内质网(ER)在糖尿病中的作用，将2型糖尿病小鼠模型秋田鼠与杂合子基因敲除小鼠或两种类型的150 kDa氧调节蛋白(ORP150)转基因小鼠交配，ORP150是位于内质网的分子伴侣。ORP150在秋田小鼠体内的系统表达改善了胰岛素不耐受，而在秋田小鼠的胰岛β细胞中独有的过表达ORP150并没有改变它们的糖耐量。胰岛素耐量试验和高胰岛素正血糖钳夹试验均显示ORP150促进葡萄糖摄取，同时抑制氧化蛋白。此外，ORP150增强了过氧化氢处理的成肌细胞的胰岛素敏感性。这些数据表明，ORP150在胰岛素敏感性中发挥重要作用，是治疗糖尿病的潜在靶点。
To determine the role of the endoplasmic reticulum (ER) in diabetes, Akita mice, a mouse model of type 2 diabetes, were mated with either heterozygous knockout mice or two types of transgenic mice of 150-kDa oxygen-regulated protein (ORP150), a molecular chaperone located in the ER. Systemic expression of ORP150 in Akita mice improves insulin intolerance, whereas the exclusive overexpression of ORP150 in pancreatic beta-cells of Akita mice did not change their glucose tolerance. Both an insulin tolerance test and hyperinsulinemiceuglycemic clamp revealed that ORP150 enhanced glucose uptake, accompanied by suppression of oxidized protein. Furthermore, ORP150 enhanced the insulin sensitivity of myoblast cells treated with hydrogen peroxide. These data suggest that ORP150 plays an important role in insulin sensitivity and is a potential target for the treatment of diabetes.