Effect of Rosiglitazone on the Differential Expression of Diabetes-associated Proteins in

The insulin sensitizer drug, rosiglitazone, has been shown to have a protective effect on pancreatic islet cell struc-ture 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 re-search 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-di-mensional 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 mod-ulated significantly (p < 0.05) by the rosiglitazone treat-ment of the obese mice. The identity of these differentially expressed proteins was made using mass spectrometric analysis and provided evidence that differential expres-sion of actin-binding proteins may be an important aspect of defective islet function. Rosiglitazone increased car-boxypeptidase B expression in both lep/lep and normal mice suggesting that this might be an independent effect of rosiglitazone that contributes to improved insuli