Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.

Exercise training is known to exert multiple beneficial effects including renal protection in type 2 diabetes mellitus and obesity. However, the mechanisms regulating these actions remain unclear. The present study evaluated the effects of chronic running exercise on the early stage of diabetic nephropathy, focusing on nitric oxide synthase (NOS), oxidative stress and glycation in the kidneys of Zucker diabetic fatty (ZDF) rats. Male ZDF rats (6 weeks old) underwent forced treadmill exercise for 8 weeks (Ex-ZDF). Sedentary ZDF (Sed-ZDF) and Zucker lean (Sed-ZL) rats served as controls. Exercise attenuated hyperglycemia (plasma glucose; 242 ± 43 mg/dL in Sed-ZDF and 115 ± 5 mg/dL in Ex-ZDF) with increased insulin secretion (plasma insulin; 2.3 ± 0.7 and 5.3 ± 0.9 ng/mL), reduced albumin excretion (urine albumin; 492 ± 70 and 176 ± 11 mg/g creatinine) and normalized creatinine clearance (9.7 ± 1.4 and 4.5 ± 0.8 mL/min per body weight) in ZDF rats. Endothelial (e) and neuronal (n) NOS expression in kidneys of Sed-ZDF rats were lower compared with Sed-ZL rats (p<0.01), while both eNOS and nNOS expression were upregulated by exercise (p<0.01). Furthermore, exercise decreased NADPH oxidase activity, p47phox expression (p<0.01) and α-oxoaldehydes (the precursors for advanced glycation end products) (p<0.01) in the kidneys of ZDF rats. Additionally, morphometric evidence indicated renal damage was reduced in response to exercise. These data suggest that upregulation of NOS expression, suppression of NADPH oxidase and α-oxoaldehydes in the kidneys may, at least in part, contribute to the renal protective effects of exercise in the early progression of diabetic nephropathy in ZDF rats. Moreover, this study supports the theory that chronic aerobic exercise could be recommended as an effective non-pharmacological therapy for renoprotection in the early stages of type 2 diabetes mellitus and obesity

Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells

International audienc

Effects of chronic running exercise on NADPH oxidase activity and p47^phox protein expression in the renal cortex of Zucker diabetic fatty rats.

<p>(A) NADPH oxidase activity was measured as an index of O₂^•– generation in the renal cortex of sedentary lean Zucker diabetic fatty (ZDF) rats (Sed-ZL), sedentary ZDF rats (Sed-ZDF) and aerobic treadmill exercised ZDF rats (Ex-ZDF) groups. (B) Protein expression of the p47^phox in the renal cortex of Sed-ZL, Sed-ZDF and Ex-ZDF groups were examined by western blot analysis. Top panels depict representative immunoblots from the different groups. The intensities of the p47^phox bands (47 kDa) for the protein were normalized against <i>β</i>-actin (40 kDa). The intensity of the band in the Sed-ZL group was assigned a value of 1. Values are means ± SEM (<i>n</i> = 5/group). ** <i>p</i><0.01 compared with the Sed-ZL group; ^††<i>p</i><0.01 compared with the Sed-ZDF group.</p

Effects of chronic running exercise on plasma parameters, urine volume, urine parameters, and systolic blood pressure in Zucker diabetic fatty rats.

<p>Sed-ZL, sedentary Zucker lean rats; Sed-ZDF, sedentary Zucker diabetic fatty rats; Ex-ZDF, treadmill exercised Zucker diabetic fatty rats.</p><p>* <i>p</i> < 0.05,</p><p>** <i>p</i> < 0.01 compared with Sed-ZL group.</p><p>^†<i>p</i> < 0.05,</p><p>^††<i>p</i> < 0.01 compared with Sed-ZDF group.</p><p>Values are mean ± SEM (<i>n</i> = 5/group).</p><p>Effects of chronic running exercise on plasma parameters, urine volume, urine parameters, and systolic blood pressure in Zucker diabetic fatty rats.</p

Effects of chronic running exercise on water intake, food intake and body weight over 8 weeks in Zucker diabetic fatty rats.

<p>(A) The water intake, (B) food intake and (C) body weight were measured weekly for 8 weeks in sedentary lean Zucker diabetic fatty (ZDF) rats (Sed-ZL), sedentary ZDF rats (Sed-ZDF) and aerobic treadmill exercised ZDF rats (Ex-ZDF) groups. Values are means ± SEM (<i>n</i> = 5/group). * <i>p</i><0.05, ** <i>p</i><0.01 compared with the Sed-ZL group; ^†<i>p</i><0.05, ^††<i>p</i><0.01 compared with the Sed-ZDF group.</p

Effects of chronic running exercise on nitrotyrosine protein expression in the renal cortex and outer medulla of Zucker diabetic fatty rats.

<p>Protein expression of the nitrotyrosine in the renal cortex (A) and outer medulla (B) of sedentary lean Zucker diabetic fatty (ZDF) rats (Sed-ZL), sedentary ZDF rats (Sed-ZDF) and aerobic treadmill exercised ZDF rats (Ex-ZDF) groups were examined by western blot analysis. Top panels depict representative immunoblots from the different groups. The intensities of the nitrotyrosine bands (70 kDa) for the protein were normalized against that of <i>β</i>-actin (40 kDa). The intensity of the band in the Sed-ZL group was assigned a value of 1. Values are means ± SEM (<i>n</i> = 5/group). ** <i>p</i><0.01 compared with the Sed-ZL group; ^†<i>p</i><0.05, ^††<i>p</i><0.01 compared with the Sed-ZDF group.</p

Effects of chronic running exercise on the intra-peritoneal glucose tolerance test in Zucker diabetic fatty rats.

<p>(A) Plasma glucose and (B) plasma insulin levels were measured by intra-peritoneal glucose tolerance test (IPGTT) at 4 days after the last exercise session and after 5 h of fasting in sedentary lean Zucker diabetic fatty (ZDF) rats (Sed-ZL), sedentary ZDF rats (Sed-ZDF) and aerobic treadmill exercised ZDF rats (Ex-ZDF) groups. (C) Homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), (D) HOMA for insulin sensitivity (HOMA-IS) and (E) HOMA for β-cell function (HOMA-β) were calculated by IPGTT data in Sed-ZL, Sed-ZDF and Ex-ZDF groups. Values are means ± SEM (<i>n</i> = 5/group). * <i>p</i><0.05, ** <i>p</i><0.01 compared with the Sed-ZL group; ^†<i>p</i><0.05, ^††<i>p</i><0.01 compared with the Sed-ZDF group.</p