Inhibition of IRS-1 function by serine phosphorylation represents a mechanism of post-receptor insulin resistance. It is well known that activation of serine kinase JNK (JUN N-terminal Kinase) leads to insulin resistance through this mechanism. In study of obese-related JNK activation, ER stress was found to be a risk factor for JNK activation in obese mice. The study was published in Science in 2004. If this hypothesis is right, chemical inhibitors for ER stress should be able to improve insulin sensitivity in obese mice. This possibility receives support from a new study published in the current issue of Science. This new study is from the same research group. Instead of adipose tissue in the earlier study, the liver is the focus in this new study for improvement of insulin sensitivity by the ER stress inhibitors. Attached are the PDF files of both studies.

ER stress in IR in 2004

ER stress inhibitor in 2006

By Jianping at PBRC
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Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225) 763-3163
Fax: (225) 763-2525
E-mail: yej@pbrc.edu