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

Molecular and Cellular Endocrinology
Stella Liong, Martha Lappas

Abstract

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 IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, 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.

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Citations

Mar 8, 2018·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Z YeZ Su
Sep 29, 2017·Journal of Molecular Endocrinology·Penny AhlstromGary Sweeney
Jan 4, 2017·PloS One·Augusto SchneiderMichal M Masternak
Jun 6, 2020·Dose-response : a Publication of International Hormesis Society·Weihong FengYang Mi
Nov 8, 2018·International Journal of Molecular Sciences·Brittany L Moyce, Vernon W Dolinsky
Oct 20, 2018·International Journal of Molecular Sciences·Katarzyna E Skórzyńska-DziduszkoBożena Leszczyńska-Gorzelak
May 5, 2021·Acta Physiologica·Marcelo CornejoLuis Sobrevia
Jul 19, 2021·Biochemical and Biophysical Research Communications·Hengting ChenXinlong Ma

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