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Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 shedding in db/db diabetic mice.
Somineni, Hari K; Boivin, Gregory P; Elased, Khalid M.
Afiliação
  • Somineni HK; Departments of Pharmacology and Toxicology Pathology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio 45435, USA Veterans Affairs Medical Center, Cincinnati, Ohio 45220, USA.
J Endocrinol ; 221(2): 235-51, 2014 May.
Article em En | MEDLINE | ID: mdl-24756098
Angiotensin II (Ang II) is involved in induction and progression of renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be renoprotective by degrading Ang II to Ang-(1-7). A disintegrin and metalloproteinase 17 (ADAM17)-mediated shedding of renal ACE2 contribute to diabetic nephropathy pathogenesis. Lifestyle modification and metformin are recommended as initial therapies for most patients with type 2 diabetes. The aim of this study was to investigate whether exercise training and/or metformin improve glucose homeostasis and albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice. Seven-week-old normal and db/db mice were subjected either to a sedentary existence or exercise training with and without metformin (150 mg/kg per day) for 10 weeks. Exercise training significantly lowered blood glucose, urinary albumin and ACE2 excretion in db/db mice. ADAM17 and ACE2 proteins were co-localized in cortical tubules of the kidney, indicating a possible interaction. Metformin treatment was effective in lowering hyperglycemia only during the first 2 weeks of treatment. Increased renal ADAM17 in 17-week-old db/db mice was corrected by physical exercise but not metformin. In addition, exercise training reduced plasma triglycerides and enhanced insulin levels of db/db mice. In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein. Urinary ACE2 could serve as a prognostic tool for the progression of kidney damage and its attenuation by exercise may partially contribute to its renal protection.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Peptidil Dipeptidase A / Diabetes Mellitus Experimental / Albuminúria / Terapia por Exercício Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Condicionamento Físico Animal / Peptidil Dipeptidase A / Diabetes Mellitus Experimental / Albuminúria / Terapia por Exercício Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article