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

Nolan, Anna
Wang, Steven
Sennitt, Matthew V
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Published in Molecular and Cellular Proteomics. 2002, vol. 1, no. 7, p. 509-16
Abstract 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.
Keywords AnimalsElectrophoresis, Gel, Two-DimensionalFemaleGlucose/metabolismGlucose Tolerance TestHypoglycemic Agents/pharmacologyIslets of Langerhans/chemistry/drug effects/metabolismMiceMice, Inbred C57BLMice, ObesePhenotypeProtein Array AnalysisProteins/metabolismThiazoles/pharmacologyThiazolidinediones
PMID: 12239279
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Research group Groupe de Protéomique biomédicale (635)
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SANCHEZ, Jean-Charles et al. Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice. In: Molecular and Cellular Proteomics, 2002, vol. 1, n° 7, p. 509-16. doi: 10.1074/mcp.m200033-mcp200 https://archive-ouverte.unige.ch/unige:37239

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Deposited on : 2014-06-10

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