Insulinotropic and Anti-Inflammatory Effects of Rosiglitazone in Experimental Autoimmune Diabetes

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The Review of Diabetic Studies,2005,2,3,146-156.
Published:November 2005
Type:Original Article
Author(s) affiliations:

Wageh M. Awara1, Alaa E. El-Sisi1, Mohamed El-Refaei2, Mona M. El-Naa1, Karima El-Desoky3

1Department of Pharmacology/Toxicology, College of Pharmacy, University of Tanta, Egypt.

2Department of Biochemistry, Genetic Engineering and Biotechnology Research Institute, Minofia University, Egypt.

3Department of Pathology, Faculty of Medicine, University of Tanta, Egypt.


Cytokines and nitric oxide (NO) are involved in the pathogenesis of autoimmune diabetes mellitus (DM). Rosiglitazone is an insulin-sensitizing drug that is a ligand for the nuclear receptor peroxisome proliferator-activated receptorgamma (PPAR-γ). The anti-inflammatory and immunomodulating properties of PPAR-γ have been documented. The aim of this study is to investigate the effectiveness of rosiglitazone in autoimmune DM and to clarify the possible mechanism(s) involved. Autoimmune DM was induced in adult male Balb/c mice by co-administration of cyclosporin A and multiple low doses of streptozotocin. Diabetic mice were treated daily with rosiglitazone (7 mg/kg, p.o.) for 21 days. Blood glucose level (BGL), serum insulin level and pancreatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and NO were measured. Histopathological examination and immunohistochemical determination of CD4 and CD8 T lymphocytes in the pancreatic islets were performed. In addition, analysis of pancreatic protein expression was carried out. The results showed that rosiglitazone treatment resulted in a significant decrease in the BGL and the pancreatic levels of TNF-α, IFN-γ and NO compared to diabetic mice. The serum insulin level was significantly increased after rosiglitazone treatment compared to diabetic mice. The destroyed pancreatic islets were regenerated and became free from both CD4 and CD8 T cells after treatment. Furthermore, many changes in pancreatic protein expression were observed. These results suggest that rosiglitazone has a beneficial effect in the treatment of autoimmune diabetes, an effect that seemed to be a secondary consequence of its anti-inflammatory and immunomodulating properties and might be reflected at the level of protein expression.