Reduced Activation of Phosphatidylinositol-3 Kinase and Increased Serine 636 Phosphorylation of Insulin Receptor Substrate-1 in Primary Culture of Skeletal Muscle Cells From Patients With Type 2 Diabetes

• DOI: 10.2337/diabetes.52.6.1319
• Publication Date: 2007-03-06T19:04:22Z
• Authors: Karim Bouzakri; Marina Roques; Philippe Gual; Sophie Espinosa; Fitsum Guebre-Egz...; Jean-Paul Riou; Martine Laville; Yannick Le Marcha...; Jean-François Tanti; Hubert Vidal
• Keywords: IRS1; Insulin receptor substrate

To understand better the defects in proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells primary culture. When compared with from control subjects, myotubes established patients diabetes presented same as those previously evidenced vivo biopsies, including defective stimulation phosphatidylinositol (PI) 3-kinase activity, decreased association PI receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation stimulation. In contrast to IRS-1, through IRS-2 was not altered. Investigating causes found a more than twofold increase basal on serine 636 diabetes. Concomitantly, there higher mitogen-activated protein kinase (MAPK) activity these cells, inhibition MAPKs PD98059 strongly level phosphorylation. These results suggest that might be involved subsequent alteration insulin-induced activation. Moreover, increased MAPK seems play role residue cells.