title: Chronic Running Exercise Alleviates Early Progression of Nephropathy with Upregulation of Nitric Oxide Synthases and Suppression of Glycation in Zucker Diabetic Rats.
abstract: 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.
authors.affiliation: Department of Miyagi Community Health Promotion, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan; Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kakihana
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Tohoku University, Sendai, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sato
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suda
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Muroya
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Gaizun
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Miyagi Community Health Promotion, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ito
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kohzuki
authors.affiliation: Department of Miyagi Community Health Promotion, Tohoku University Graduate School of Medicine, Tohoku University, Sendai, Japan; Department of Integrated Nephrology and Telemedicine, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Hideyasu
authors.initials: H
authors.lastname: Kiyomoto
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D019001:Nitric Oxide Synthase