Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women

作者：Liong Stella; Lappas Martha

来源：Molecular and Cellular Endocrinology, 2016, 425(C): 11-25.

DOI：10.1016/j.mce.2016.02.016

• ER stress
• Skeletal muscle
• Insulin resistance
• Gestational diabetes
• Inflammation

Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1 alpha, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1 alpha was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1 alpha and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1 beta-induced production of IL-6, IL-8, IL-10 and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-alpha-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-beta, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle.

• 出版日期2016-4-15