Exercise combined with metformin ameliorates diabetic kidney disease by increasing renal autophagy and reducing oxidative stress in rats with high-fat diet and streptozotocin induced diabetes

Diabetic kidney disease (DKD) is one of the common and serious complications of type 2 diabetes mellitus (T2DM). Metformin is commonly prescribed for the treatment of T2DM, while exercise is frequently recommended as adjunctive therapy. However, the therapeutic efficacy and molecular etiology of combined therapy with exercise and metformin in DKD remain to be elucidated. The present study therefore aimed to investigate the therapeutic effects and mechanisms underlying the combined effects of exercise and metformin on DKD. A rat model of T2DM was constructed by administering a high-fat diet and intraperitoneal injections of streptozotocin (30 mg/kg) for 6 weeks. The rats with T2DM exhibited reduced autophagic flux, increased oxidative stress, and morphological and structural lesions in the kidneys, compared to those of normal rats in the control group. The combination of exercise and metformin alleviated DKD, indicated by the elevation of renal autophagic flux, and a reduction in oxidative stress, renal fibrosis, and histopathological damage to the kidneys. Our findings suggested that exercise combined with metformin has a therapeutic role in DKD, and the study serves as a valuable reference for future research on the treatment of DKD.