PMID: 12765939May 27, 2003Paper

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

Diabetes
Karim BouzakriHubert Vidal

Abstract

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

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Citations

Aug 10, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Cyrille DebardHubert Vidal
Aug 22, 2007·Cell Biochemistry and Biophysics·Håkan K R Karlsson, Juleen R Zierath
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Jun 18, 2009·American Journal of Physiology. Endocrinology and Metabolism·Louis Hue, Heinrich Taegtmeyer
Jun 29, 2012·American Journal of Physiology. Endocrinology and Metabolism·Guangzhi ChenDao Wen Wang
Feb 26, 2009·American Journal of Physiology. Endocrinology and Metabolism·Xianling LiuFeng Liu
Oct 16, 2008·American Journal of Physiology. Endocrinology and Metabolism·Sathyaseelan S Deepa, Lily Q Dong
Feb 3, 2007·The Journal of Clinical Investigation·Olivier Le BacquerNahum Sonenberg
Apr 8, 2010·Endocrinology·Kartik ShankarThomas M Badger
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Jan 28, 2014·Biochemical and Biophysical Research Communications·Mohammad Shamsul Ola
Jul 6, 2014·Nutrition·Anik BoudreauZ Elizabeth Floyd

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