Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
Dysregulation of insulin receptor substrate 2 in β cells and brain causes obesity and diabetes
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DOI：
10.1172/jci200422217
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发表时间：
2004-10-01
影响因子：
15.9
通讯作者：
White, MF
中科院分区：
文献类型：
--
作者：
Lin, XY;Taguchi, A;White, MF
肥胖和引起糖尿病的P细胞衰竭之间的分子联系很难确定。本研究表明，小鼠胰腺P细胞和大脑部分（包括下丘脑）中胰岛素受体底物2 （Irs2）的条件敲除会增加食欲、瘦体重和胖体重、线性生长和胰岛素抵抗，并最终发展为糖尿病。当老鼠长到6到10个月大时，糖尿病就消失了：表达Irs2的功能性P细胞在胰腺中重新繁殖，恢复了足够的P细胞功能，以补偿肥胖老鼠的胰岛素抵抗。因此，Irs2信号可以促进成年P细胞的再生和营养平衡的中枢控制，从而预防小鼠的肥胖和糖尿病。
The molecular link between obesity and P cell failure that causes diabetes is difficult to establish. Here we show that a conditional knockout of insulin receptor substrate 2 (Irs2) in mouse pancreas P cells and parts of the brain-including the hypothalamus-increased appetite, lean and fat body mass, linear growth, and insulin resistance that progressed to diabetes. Diabetes resolved when the mice were between 6 and 10 months of age: functional P cells expressing Irs2 repopulated the pancreas, restoring sufficient P cell function to compensate for insulin resistance in the obese mice. Thus, Irs2 signaling promotes regeneration of adult P cells and central control of nutrient homeostasis, which can prevent obesity and diabetes in mice.