Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Diabetes Publish Ahead of Print published online ahead of print March 14, 2007
DOI: 10.2337/db06-1355
This Article
Right arrow Full Text (PDF)
Right arrow Online Only Appendix
Right arrow All Versions of this Article:
db06-1355v1
db06-1355v2
56/6/1508    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yi, Z.
Right arrow Articles by Mandarino, L. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yi, Z.
Right arrow Articles by Mandarino, L. J.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Original Research

Global Assessment of Regulation of Phosphorylation of Insulin Receptor Substrate (IRS)-1 by Insulin in Vivo in Human Muscle

Zhengping Yi1,2, Paul Langlais1,3, Elena A. De Filippis1,2, Moulun Luo1,2, Charles R. Flynn1, Stefanie Schroeder1, Susan T. Weintraub4, Rebekka Mapes1,5, and Lawrence J. Mandarino1,2,3

1Center for Metabolic Biology, Arizona State University, Tempe, Arizona
2School of Life Sciences, Arizona State University, Tempe, Arizona
3Department of Kinesiology, Arizona State University, Tempe, Arizona
4Department of Biochemistry, The University of Texas Health Science Center, San Antonio, Texas
5Department of Physiology, The University of Texas Health Science Center, San Antonio, Texas

Correspondence: lawrence.mandarino{at}asu.edu

Objective.: Research has focused on Insulin Receptor Substrate-1 (IRS-1) as a locus for insulin resistance. Tyrosine phosphorylation of IRS-1 initiates insulin signaling; serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Of 1242 amino acids in IRS-1, 242 are serine/threonine. Serine/threonine phosphorylation of IRS-1 is affected by many factors, including insulin. The purpose of this study was to perform global assessment of phosphorylation of serine/threonine residues in IRS-1 in vivo in humans.

Research Design and Methods.: In this report we describe our use of capillary HPLC-electrospray tandem mass spectrometry to identify/quantify site-specific phosphorylation of IRS-1 in human vastus lateralis muscle obtained by needle biopsy, basally and after insulin infusion in four healthy volunteers.

Results.: Twenty-two serine/threonine phosphorylation sites were identified; fifteen were quantified. Three sites had not been identified previously (Thr495, Ser527, and S1005). Insulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 (2.6 ± 0.4, 2.9 ± 0.8, 2.1 ± 0.3, 1.6 ± 0.1, 1.3 ± 0.1, and 1.3 ± 0.1 fold, respectively, compared to basal; P < 0.05); phosphorylation of Ser348, Thr446, Thr495, and Ser1005 decreased (0.4 ± 0.1, 0.2 ± 0.1, 0.1 ± 0.1, and 0.3 ± 0.2 fold, respectively; P < 0.05).

Conclusions.: These results provide an assessment of IRS-1 phosphorylation in vivo and show that insulin has profound effects on IRS-1 serine/threonine phosphorylation in healthy humans.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2007 by the American Diabetes Association.