Synergistic Renoprotective Effects of Moderate‐Intensity Resistance Training and Vitamin D Supplementation on a Type 2 Diabetic Nephropathy Rat Model

Vitamin D (VD) supplementation and resistance exercise synergistically improve diabetic nephropathy in type 2 diabetes mellitus (T2DM). However, the effects of varying exercise intensities and underlying mechanisms remain unclear. This study systematically examined the combined effects of low-intensity resistance training with VD (LRV), moderate-intensity resistance training with VD (MRV), and high-intensity resistance training with VD (HRV) in a T2DM rat model. We aimed to determine the optimal exercise intensity combined with VD supplementation and elucidate its associated molecular mechanisms. All combined interventions significantly improved glucose metabolism and insulin sensitivity, with the most pronounced effects observed in the MRV group. MRV was most effective in restoring renal function, as indicated by reductions in blood urea nitrogen and serum creatinine. MRV also significantly inhibited diabetes-induced renal fibrosis and inflammation, demonstrated by decreased TNF-α, IL-1β, and IL-6 levels. Mechanistically, MRV upregulated renal VD receptor (VDR) expression and inhibited the p38 mitogen-activated protein kinase (MAPK) and ERK1/2 signaling pathways, resulting in reduced renal fibrosis and local inflammation. Comparative analysis indicated that MRV produced the most effective synergistic outcome, with an optimal intensity threshold. These results suggest that MRV is a potential non-pharmacological strategy to alleviate complications of type 2 diabetes via the VDR-MAPK signaling pathway, with important implications for clinical exercise prescription.