Supplementary Material for: Endurance exercise training-attenuated diabetic kidney disease with muscle weakness in spontaneously diabetic Torii fatty rats.

Abstract Background The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. Methods Eight-week-old SDT fatty rats (n = 12) and Sprague–Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise four times a week from ages 8 to 16 weeks. Results The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. Conclusion Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels.

研究背景与目的 本研究以合并肥胖、高血压与高脂血症的2型糖尿病动物模型——雄性自发性糖尿病Torii（SDT）肥胖大鼠为对象，旨在评估耐力运动训练对伴肌肉无力的糖尿病肾病（DKD）的保护作用。
实验方法 将12只8周龄SDT肥胖大鼠与10只8周龄Sprague-Dawley（SD）大鼠随机分为运动组（SDT-Ex组：n=6，SD-Ex组：n=5）与静坐对照组（SDT-Cont组：n=6，SD-Cont组：n=5）。自8周龄至16周龄，各组每周进行4次常规跑台运动训练。
实验结果 耐力运动可缓解高血压与高脂血症，且在不影响血糖水平的前提下抑制肾脏参数水平升高。在SDT肥胖大鼠中，运动可阻止肾皮质浅层与中间层间质出现肾脏形态学异常。运动可显著上调SDT肥胖大鼠肾小球内原本表达下调的内皮型一氧化氮合酶（endothelial nitric oxide synthase）的表达水平。运动可上调肾脏中与脂肪酸代谢相关的中链酰基辅酶A脱氢酶（medium-chain acyl-CoA dehydrogenase）及过氧化物酶体增殖物激活受体γ辅激活因子1α（peroxisome proliferator-activated receptor γ coactivator-1α）的表达水平。此外，运动可提升SDT肥胖大鼠的肌肉力量，增加其趾长伸肌的肌肉重量以及IIb型肌纤维的横截面积。
研究结论 针对2型糖尿病的耐力运动训练，可通过改善内皮功能异常、增强脂肪酸代谢，同时缓解高血压、高脂血症与肌肉无力，且该保护作用不依赖于血糖水平，从而改善糖尿病肾病（DKD）。