title: Effect of rosiglitazone on the differential expression of diabetes-associated proteins in pancreatic islets of C57Bl/6 lep/lep mice.
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.
authors.affiliation: Geneva Proteomics Center, Central Clinical Chemistry Laboratory, Geneva University Hospital, 1211 Geneva 14, Switzerland. sanchez@dim.hcuge.ch
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
authors.forename: Véronique
authors.initials: V
authors.lastname: Converset
authors.forename: Anna
authors.initials: A
authors.lastname: Nolan
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schmid
authors.forename: Steven
authors.initials: S
authors.lastname: Wang
authors.forename: Manfred
authors.initials: M
authors.lastname: Heller
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Sennitt
authors.forename: Denis F
authors.initials: DF
authors.lastname: Hochstrasser
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cawthorne
mesh_terms: D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D010641:Phenotype; D040081:Protein Array Analysis; D011506:Proteins / Q000378:metabolism*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones
chemical_list: D007004:Hypoglycemic Agents; D011506:Proteins; D013844:Thiazoles; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005947:Glucose