Effect of rosiglitazone on the differential expression of diabetes associated proteins in pancreatic islets of C57Bl/6 lep/lep mice

doi:10.1074/mcp.M200033-MCP200

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Submitted on June 4, 2002
Revised on July 18, 2002
Accepted on July 19, 2002

Effect of rosiglitazone on the differential expression of diabetes associated proteins in pancreatic islets of C57Bl/6 lep/lep mice

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

Geneva Proteomics Center, Geneva University Hospital, Geneva 14, Geneva 1211

Corresponding Author: sanchez{at}dim.hcuge.ch

The insulin sensitiser 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 sensitiser drug BRL49653, rosiglitazone. It normalised 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 over-expressed and 6 under-expressed proteins were significant (p<0.05) between lep/lep and lean mice and 4 were significantly (p<0.05) modulated 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.

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