SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B
SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B
复制标题
SIRT1 通过抑制 PTP1B 来改善胰岛素抵抗条件下的胰岛素敏感性。
DOI：
10.1016/j.cmet.2007.08.014
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发表时间：
2007-10-01
期刊：
影响因子：
29
通讯作者：
Zhai, Qiwei
中科院分区：
文献类型：
--
作者：
Sun, Cheng;Zhang, Fang;Zhai, Qiwei
胰岛素抵抗通常被认为是导致2型糖尿病发展的最关键因素。据报道SIRT 1参与葡萄糖代谢和胰岛素分泌过程。然而，SIRT 1是否直接参与胰岛素敏感性仍然是未知的。在这里，我们发现SIRT 1在胰岛素抵抗细胞和组织中下调，并且SIRT 1的敲低或抑制诱导胰岛素抵抗。此外，SIRT 1表达增加改善胰岛素敏感性，特别是在胰岛素抵抗条件下。同样，白藜芦醇，一种SIRT 1激活剂，在体外以SIRT 1依赖的方式增强胰岛素敏感性，并在体内以2.5 mg/kg/天的剂量减弱高脂饮食诱导的胰岛素抵抗。进一步的研究表明，SIRT 1对胰岛素抵抗的作用是通过在染色质水平上抑制PTP 1B转录来介导的。总之，SIRT 1改善胰岛素敏感性的发现对解决胰岛素抵抗和2型糖尿病有意义。
Insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes. SIRT1 has been reported to be involved in the processes of glucose metabolism and insulin secretion. However, whether SIRT1 is directly involved in insulin sensitivity is still largely unknown. Here we show that SIRT1 is down-regulated in insulin-resistant cells and tissues and that knockdown or inhibition of SIRT1 induces insulin resistance. Furthermore, increased expression of SIRT1 improved insulin sensitivity, especially under insulin-resistant conditions. Similarly, resveratrol, a SIRT1 activator, enhanced insulin sensitivity in vitro in a SIRT1-dependent manner and attenuated high-fat-diet-induced insulin resistance in vivo at a dose of 2.5 mg/kg/day. Further studies demonstrated that the effect of SIRT1 on insulin resistance is mediated by repressing PTP1B transcription at the chromatin level. Taken together, the finding that SIRT1 improves insulin sensitivity has implications toward resolving insulin resistance and type 2 diabetes.