Insulinotropic and anti-inflammatory effects of rosiglitazone in experimental autoimmune diabetes
| Autor: | Alaa E. El-Sisi, Wageh M. Awara, Mohamed F. El-Refaei, Karima I El-Desoky, Mona M. El-Naa |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
business.industry Endocrinology Diabetes and Metabolism Pancreatic islets Streptozotocin Nitric oxide Original Data chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Internal medicine Cyclosporin a Internal Medicine medicine Cytotoxic T cell Tumor necrosis factor alpha Rosiglitazone business CD8 medicine.drug |
| Zdroj: | The review of diabetic studies : RDS. 2(3) |
| ISSN: | 1614-0575 |
| Popis: | 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 receptor-gamma (PPAR-gamma). The anti-inflammatory and immunomodulating properties of PPAR-gamma 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-alpha), interferon-gamma (IFN-gamma) 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-alpha, IFN-gamma 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|