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Metformin Protects Renal Function in Type 2 Diabetic Nephropathy: Regulation of Insulin Signaling in the Rat Model

The present study was aimed to investigate the protective role of metformin in type 2 diabetic nephropathic rats and elucidate regulation of unwanted insulin signaling in the kidney as the underlying mechanism. Diabetes mellitus was established in male Sprague Dawley rats by a single intraperitoneal injection of 40 mg/kg streptozotocin. A sustained level of blood glucose over 16.7 mM was defined as type 2 diabetes mellitus in this study. Rats were randomly classified into the normal group, diabetes mellitus group, diabetes mellitus plus low-dose and high-dose metformin groups (100 and 200 mg/kg orally). Rats received treatment for 12 weeks after which all rats were sacrificed and kidney samples were collected. The samples were dissected and prepared for the observation of structural changes of renal glomerular podocytes between the groups microscopically. The expressions of IRS-1, Akt, nephrin, desmin, phosphatidylinositol-3-hydroxy kinase (PI3K)-p85 and extra cellular matrix were probed by western blot. Compared to the control group, the downregulated nephrin and elevated levels of desmin and collagen IV in the kidney were significantly reversed by metformin treatment. Furthermore, metformin recovered the atypical activities of insulin/PI3K-Akt signaling to the normal ranges. Metformin evidently reduced the renal damage in diabetic rats, which could be due to modulating lipid metabolism and insulin resistance.