Gemfibrozil and its combination with metformin on pleiotropic effect on IL-10 and adiponectin and anti-atherogenic treatment in insulin resistant type 2 diabetes mellitus rats

Abstract

Gemfibrozil is a PPAR-α ligand that inhibits the progression of atherosclerosis in insulin resistance type 2 diabetes mellitus (IR type 2 DM). Gemfibrozil, poor anti-hyperglycemic combined with metformin, evaluated for MMP-9, IL-10 and adiponectin beyond glycemic control. IR type 2 DM induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. IR type 2 DM rats at 6-week age treated for 8 weeks with (1) gemfibrozil (140 mg/kg od) and (2) gemfibrozil (70 mg/kg bid) + metformin (60 mg/kg bid). At the end, risk parameters like MMP-9, IL-10 and adiponectin were evaluated by ELISA kits. Gemfibrozil reduced the MMP-9 levels (-25.740 %) (106.772 ± 7.201 ng/ml vs. 80.231 ± 7.023 ng/ml, P < 0.01); increased adiponectin (68.321 %) (8.781 ± 1.111 μg/ml vs. 14.782 ± 1.055 μg/ml) and IL-10 (155.687 %) (334.208 ± 26.307 pg/ml vs. 853.472 ± 23.172 pg/ml, P < 0.001), but poor glycemic control (-6.169 %) (167.5 ± 16.037 vs. 157.167 ± 3.911, P = ns), hence combined with metformin showed synergistic activity, reduced the MMP-9 levels (-16.992 %) (106.772 ± 7.201 ng/ml vs. 89.941 ± 8.636 ng/ml, P < 0.05) and increased adiponectin (39.870 %) (8.781 ± 1.111 μg/ml vs. 12.282 ± 0.782 μg/ml) and, IL-10 (80.136 %) (334.208 ± 26.307 pg/ml vs. 602.029 ± 39.668 pg/ml, P < 0.01) had good glycemic control (-28.856 %) (167.5 ± 16.037 mg/dl vs. 129.167 ± 4.214 mg/dl, P < 0.05). Gemfibrozil plus metformin decrease MMP-9, increase IL-10 and adiponectin acting as anti-atherogenic, anti-inflammatory and immunomodulatory in IR type 2 DM.