The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension
The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension
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DOI：
10.1152/ajprenal.00145.2014
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发表时间：
2014-08-01
影响因子：
4.2
通讯作者：
Hugo, Christian
中科院分区：
文献类型：
--
作者：
Gembardt, Florian;Bartaun, Christoph;Hugo, Christian
糖尿病肾病是西方世界人类终末期肾病的主要原因。最近开发的 Na+-葡萄糖协同转运蛋白 2 (SGLT2) 抑制剂通过增强葡萄糖排泄提供了一种新的抗糖尿病疗法。这种策略是否对 2 型糖尿病肾病的发展产生有益影响目前仍不清楚。我们研究了特定 SGLT2 抑制剂恩格列净在 BTBR 中的作用。 Cg-Lep<ob>/WiscJ (BTBR ob/ob) 小鼠，自发发展为 2 型糖尿病肾病。在第一个实验中，BTBR ob/ob 小鼠接受含有 300 ppm 恩格列净的饮食或等热量的安慰剂饲料，持续 12 周。在第二个实验中，BTBR ob/ob小鼠接受1μg.kg体重(-1).天(-1) ANG II以诱导动脉高血压，并分为相同的两个饮食组，持续6周。在这两个实验中，恩格列净治疗增强了糖尿，从而降低了血糖。与高血压无关，恩格列净可降低糖尿病小鼠的蛋白尿。然而，恩格列净治疗仅影响无高血压的 BTBR ob/ob 小鼠的糖尿病相关肾小球肥大、肾脏炎症标志物和系膜基质扩张。总之，恩格列净表现出显着的抗高血糖作用，可显着改善患有和不患有高血压的 BTBR ob/ob 小鼠糖尿病肾病的早期特征。
Diabetic nephropathy is the leading cause of end-stage renal disease in humans in the Western world. The recent development of Na+-glucose cotransporter 2 (SGLT2) inhibitors offers a new antidiabetic therapy via enhanced glucose excretion. Whether this strategy exerts beneficial effects on the development of type 2 diabetic nephropathy is still largely unclear. We investigated the effects of the specific SGLT2 inhibitor empagliflozin in BTBR. Cg-Lep < ob >/WiscJ (BTBR ob/ob) mice, which spontaneously develop type 2 diabetic nephropathy. In the first experiment, BTBR ob/ob mice received either a diet containing 300 ppm empagliflozin or equicaloric placebo chow for 12 wk. In the second experiment, BTBR ob/ob mice received 1 mu g.kg body wt(-1).day(-1) ANG II to induce arterial hypertension and were separated into the same two diet groups for 6 wk. In both experiments, empagliflozin treatment enhanced glucosuria, thereby lowering blood glucose. Independently of hypertension, empagliflozin reduced albuminuria in diabetic mice. However, empagliflozin treatment affected diabetes-related glomerular hypertrophy, markers of renal inflammation, and mesangial matrix expansion only in BTBR ob/ob mice without hypertension. In summary, empagliflozin demonstrated significant anti-hyperglycemic effects, differentially ameliorating early features of diabetic nephropathy in BTBR ob/ob mice with and without hypertension.