MCP Waters-The Science of What's Possible
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Originally published In Press as doi:10.1074/mcp.M200033-MCP200 on July 19, 2002.
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Molecular & Cellular Proteomics 1:509-516, 2002.
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Effect of Rosiglitazone on the Differential Expression of Diabetes-associated Proteins in Pancreatic Islets of C57Bl/6 lep/lep Mice*

Jean-Charles Sanchez{ddagger},§, Véronique Converset{ddagger}, Anna Nolan, Gerhard Schmid{ddagger}, Steven Wang, Manfred Heller{ddagger}, Matthew V. Sennitt, Denis F. Hochstrasser{ddagger} and Michael A. Cawthorne

{ddagger} Geneva Proteomics Center, Central Clinical Chemistry Laboratory, Geneva University Hospital, 1211 Geneva 14, Switzerland
Clore Laboratory, School of Science, University of Buckingham, Buckingham MK18 1EG, United Kingdom

The insulin sensitizer drug, rosiglitazone, has been shown to have a protective effect on pancreatic islet cell structure and function in animal models of type 2 diabetes. The identification of new molecular targets associated both with islet cell dysfunction and protection is a crucial research goal. In the present study, a proteomics approach has been used to identify such targets. Obese C57Bl/6J lep/lep mice and lean littermates were given the insulin sensitizer drug BRL49653, rosiglitazone. It normalized the impaired glucose tolerance in lep/lep mice but had no significant effect on glucose tolerance in the lean mice. Pancreatic islet polypeptides were arrayed by a two-dimensional gel electrophoresis system that separated more than 2500 individual spots. Three overexpressed and six underexpressed proteins were significant (p < 0.05) between lep/lep and lean mice, and four were modulated significantly (p < 0.05) by the rosiglitazone treatment of the obese mice. The identity of these differentially expressed proteins was made using mass spectrometric analysis and provided evidence that differential expression of actin-binding proteins may be an important aspect of defective islet function. Rosiglitazone increased carboxypeptidase B expression in both lep/lep and normal mice suggesting that this might be an independent effect of rosiglitazone that contributes to improved insulin processing.

§ To whom correspondence should be addressed: Geneva Proteomics Center, Central Clinical Chemistry Laboratory, Geneva University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. Tel.: 41-22-372-73-74; Fax: 41-22-372-73-99; E-mail: sanchez{at}dim.hcuge.ch


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