Role for sterol regulatory element binding protein-1c activation in mediating skeletal muscle insulin resistance via repression of rat insulin receptor substrate-1 transcription

Diabetologia
Yan BiDalong Zhu

Abstract

Sterol regulatory element binding protein-1c (SREBP-1c) is a master regulator of fatty acid synthase and controls lipogenesis. IRS-1 is the key insulin signalling mediator in skeletal muscle. In the present study, we investigated the role of SREBP-1c in the regulation of IRS-1 in skeletal muscle cells. L6 muscle cells were treated with palmitic acid (PA) or metformin. Adenovirus vectors expressing Srebp-1c (also known as Srebf1) and small interfering RNA (siRNA) against Srebp-1c were transfected into the L6 cells. Protein-DNA interactions were assessed by luciferase reporter analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation assay. We found that both gene and protein expression of SREBP-1c was increased in contrast to IRS-1 expression in PA-treated L6 cells. SREBP-1c overproduction decreased Irs-1 mRNA and IRS-1 protein expression in a dose-dependent manner, and suppressed the resultant insulin signalling, whereas SERBP-1c knockdown by Serbp-1c siRNA blocked the downregulation of IRS-1 induced by PA. Protein-DNA interaction studies demonstrated that SREBP-1c was able to bind to the rat Irs-1 promoter region, thereby repressing its gene transcription. Of particular importance, we found that metformi...Continue Reading

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Citations

Sep 15, 2015·Laboratory Investigation; a Journal of Technical Methods and Pathology·Carolina Gutierrez-RepisoEduardo Garcia-Fuentes
May 26, 2015·Trends in Pharmacological Sciences·Selma M SoyalWolfgang Patsch
Jul 16, 2017·Journal of Lipid Research·Jing-Jing ZhangBin Liang
Nov 25, 2017·Scientific Reports·Ilana KelseyBrendan D Manning
Mar 27, 2019·Journal of Molecular Endocrinology·Lan XuZi-Jiang Chen
Oct 19, 2017·International Journal of Molecular Medicine·Wenjuan TangYan Bi
Jan 9, 2020·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Fen XuJianping Weng

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