Interleukin-1β-Induced Insulin Resistance in Adipocytes through Down-Regulation of Insulin Receptor Substrate-1 Expression

• DOI: 10.1210/en.2006-0692
• Publication Date: 2006-10-13T10:40:20Z
• Authors: Jennifer Jager; Thierry Grémeaux; Mireille Cormont; Yannick Le Marcha...; Jean-François Tanti
• Keywords: IRS1; Insulin receptor substrate; IRS2; Proinflammatory cytokine; 3T3-L1

Inflammation is associated with obesity and insulin resistance. Proinflammatory cytokines produced by adipose tissue in could alter signaling action. Recent studies have shown a relationship between IL-1beta level metabolic syndrome or type 2 diabetes. However, the ability of to action remains be explored. We demonstrated that slightly increased Glut 1 translocation basal glucose uptake 3T3-L1 adipocytes. Importantly, we found prolonged treatment reduced insulin-induced uptake, whereas an acute had no effect. Chronic decreased expression 4 markedly inhibited its plasma membrane response insulin. This inhibitory effect was due decrease amount receptor substrate (IRS)-1 but not IRS-2 both human The IRS-1 resulted reduction tyrosine phosphorylation alteration protein kinase B activation AS160 phosphorylation. Pharmacological inhibition ERK totally IL-1beta-induced down-regulation mRNA. Moreover, activation, phosphorylation, were partially recovered after inhibitor. These results demonstrate reduces at transcriptional through mechanism dependent posttranscriptional independently activation. By targeting IRS-1, capable impairing action, thus participate concert other cytokines, development resistance