西亚试剂：SIRT1 Improves Insulin Sensitivity under Insulin-Resistant

SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B

Cheng Sun,1 Fang Zhang,1 Xinjian Ge,1 Tingting Yan,1 Xingmiao Chen,1 Xianglin Shi,1 and Qiwei Zhai1,

1 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China

Corresponding author
Qiwei Zhai
 

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 downregulated 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.

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