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

Cheng Sun, Fang Zhang, Xinjian Ge, Tingting Yan, Xingmiao Chen, Xianglin Shi, Qiwei Zhai

Research output: Contribution to journalArticlepeer-review

654 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)307-319
Number of pages13
JournalCell Metabolism
Volume6
Issue number4
DOIs
StatePublished - Oct 3 2007

Bibliographical note

Funding Information:
This study was supported by grants from the National Natural Science Foundation of China (30400083 and 30570558), the Chinese Academy of Sciences (KSCX2-2-25, KSCX2-YW-N-034, and KSCX1-YW-02), the National Basic Research Program of China (973 Program, 2006CB503900 and 2007CB914501), the Science and Technology Commission of Shanghai Municipality (04 DZ14007), and the Program of Shanghai Subject Chief Scientist. Q.Z. and X.S. are scholars of the Hundred Talents Program of the Chinese Academy of Sciences. Q.Z. is also a scholar of the Shanghai Rising-Star Program of the Science and Technology Commission of Shanghai Municipality.

Keywords

  • HUMDISEASE
  • PROTEINS

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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