High-intensity interval training induces renal injury and fibrosis in type 2 diabetic mice

Previous studies showed that high-intensity interval training (HIIT) improved fasting blood glucose and insulin resistance in type 2 diabetes mellitus (T2DM) mice. However, the effect of HIIT on the kidneys of mice with T2DM has not been examined. This study aimed to investigate the impact of HIIT on the kidneys of T2DM mice.T2DM mice were induced with a high-fat diet (HFD) and one-time 100 mg/kg streptozotocin intraperitoneal injection, and then T2DM mice were treated with 8 weeks of HIIT. Renal function and glycogen deposition were observed by serum creatinine levels and PAS staining, respectively. Sirius red staining, hematoxylin-eosin staining, and Oil red O staining were used to detect fibrosis and lipid deposition. Western blotting was performed to detect the protein levels.HIIT significantly ameliorated the body composition, fasting blood glucose, and serum insulin of the T2DM mice. HIIT also improved glucose tolerance, insulin tolerance, and renal lipid deposition of T2DM mice. However, we found that HIIT increased serum creatinine and glycogen accumulation in the kidneys of T2DM mice. Western blot analysis showed that the PI3K/AKT/mTOR signaling pathway was activated after HIIT. The expression of fibrosis-related proteins (TGF-β1, CTGF, collagen-III, α-SMA) increased, while the expression of klotho (sklotho) and MMP13 decreased in the kidneys of HIIT mice.This study concluded that HIIT induced renal injury and fibrosis, although it also improved glucose homeostasis in T2DM mice. The current study reminds us that patients with T2DM should be cautious when participating in HIIT.