The role of mTOR in the adaptation and failure of β-cells in type 2 diabetes

被引:58
作者
Leibowitz, G. [1 ]
Cerasi, E. [1 ]
Ketzinel-Gilad, A. [1 ]
机构
[1] Hadassah Hebrew Univ, Med Ctr, Endocrinol & Metab Serv, Dept Med, IL-91120 Jerusalem, Israel
关键词
beta-cell; insulin secretion; lifespan; mTOR; metabolism; rapamycin;
D O I
10.1111/j.1463-1326.2008.00952.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mimmalian target of rapamycin (mTOR) is all important nutrient sensor that plays a critical role in cellular metabolism, growth, proliferation all apoptosis and in the cellular response to oxidative stress. In addition. mOR-raptor complex. also called mammalian target of rapamycin complex 1 (mTORC1), generates an inhibitory feedback loop oil insulin receptor Substrate proteins. It was suggested that nutrient overload leads to insulin/insulin-like growth factor 1 resistance in peripheral insulin-responsive tissues and in the beta-cells through sustained activation of mTORC1. In this review. we summarize the literature oil the regulation and function of mTOR, its role in the organism's response to nutrients and its potential impact oil lifespan, insulin resistance and the metabolic adaptation to hyperglycacemia ill type 2 diabetes. We also propose a hypothesis based oil data in the literature as a,ell as data generated in our laboratory, which assigns a central positive role to mTOR in the maintenance of beta-cell function and mass in the diabetic environment.
引用
收藏
页码:157 / 169
页数:13
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