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Scientific article
English

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

Published inMolecular & cellular proteomics, vol. 1, no. 7, p. 509-516
Publication date2002
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
  • Animals
  • Electrophoresis, Gel, Two-Dimensional
  • Female
  • Glucose/metabolism
  • Glucose Tolerance Test
  • Hypoglycemic Agents/pharmacology
  • Islets of Langerhans/chemistry/drug effects/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Phenotype
  • Protein Array Analysis
  • Proteins/metabolism
  • Thiazoles/pharmacology
  • Thiazolidinediones
Citation (ISO format)
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 & cellular proteomics, 2002, vol. 1, n° 7, p. 509–516. doi: 10.1074/mcp.m200033-mcp200
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1535-9476
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