Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 shedding in db/db diabetic mice.
Daily exercise training protects against albuminuria and angiotensin converting enzyme 2 shedding in db/db diabetic mice.
复制标题
DOI：
10.1530/joe-13-0532
复制
发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Elased KM
中科院分区：
文献类型：
--
作者：
Somineni HK;Boivin GP;Elased KM
血管紧张素II（Angiotensin II，Ang II）参与了糖尿病肾损害的发生和发展。血管紧张素转化酶2（ACE 2）在肾脏中高度表达，并且已显示通过将Ang II降解为Ang-（1-7）而具有肾脏保护作用。去整合素和金属蛋白酶（ADAM 17）介导的肾脏ACE 2的脱落有助于糖尿病肾病的发病机制。生活方式改变和二甲双胍被推荐作为大多数2型糖尿病患者的初始治疗。本研究的目的是研究运动训练和/或二甲双胍是否改善db/db小鼠的葡萄糖稳态、白蛋白尿和下调肾脏ADAM 17和ACE 2脱落。7周龄的正常和db/db小鼠进行了10周的久坐或运动训练与二甲双胍（150 mg/kg/d）和不与二甲双胍（150 mg/kg/d）。运动训练显着降低血糖，尿白蛋白和ACE 2排泄在db/db小鼠。ADAM 17和ACE 2蛋白共定位于肾皮质小管，表明可能的相互作用。二甲双胍治疗仅在治疗的前2周有效降低高血糖。在17周龄db/db小鼠中增加的肾脏ADAM 17通过体育锻炼而不是二甲双胍纠正。此外，运动训练降低了db/db小鼠的血浆甘油三酯和提高了胰岛素水平。总之，运动训练单独或与二甲双胍联合可通过降低ADAM 17蛋白来预防肾脏ACE 2的脱落。尿ACE 2可作为肾损伤进展的预后工具，运动可使其衰减，这可能部分有助于其肾保护作用。
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). Disintegrin and Metalloproteinase (ADAM) 17 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 the study was to investigate whether exercise training and/or metformin improve glucose homeostasis, albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice. Seven wk old normal and db/db mice were subjected either to sedentary or exercise training with and without metformin (150 mg/kg/day) for 10 wks. 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, suggesting a possible interaction. Metformin treatment was effective in lowering hyperglycemia only during the first 2 weeks of treatment. Increased renal ADAM17 in 17 wk 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 in the progression of kidney damage and its attenuation by exercise may partially contribute to its renal protection.