Losartan modulates muscular capillary density and reverses thiazide diuretic-exacerbated insulin resistance in fructose-fed rats.
Losartan modulates muscular capillary density and reverses thiazide diuretic-exacerbated insulin resistance in fructose-fed rats.
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DOI：
10.1038/hr.2011.140
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发表时间：
2012-01
影响因子：
5.4
通讯作者：
Ito, Sadayoshi
中科院分区：
文献类型：
--
作者：
Guo, Qi;Mori, Takefumi;Jiang, Yue;Hu, Chunyan;Ohsaki, Yusuke;Yoneki, Yoshimi;Nakamichi, Takashi;Ogawa, Susumu;Sato, Hiroshi;Ito, Sadayoshi
关键词：
肾素-血管紧张素系统（RAS）参与胰岛素敏感性（IS）的发病机制。RAS在胰岛素抵抗和肌肉循环中的作用尚未阐明。因此，本研究旨在确定血管紧张素II受体阻滞剂（ARB）和/或利尿剂对果糖喂养大鼠（FFR）IS和毛细血管密度（CD）的作用机制。Sprague-Dawley大鼠喂食正常食物（对照组）或富含果糖的食物8周。在过去4周内，将FFR分配至4组：FFR组和接受噻嗪类利尿剂氢氯噻嗪（HCTZ）、ARB氯沙坦或两者联合治疗的组。在第8周通过正常血糖高胰岛素葡萄糖钳夹技术评价IS。此外，评价了趾长伸肌中的CD。FFR组的血压显著高于对照组。HCTZ、氯沙坦及其组合显著降低血压。FFR组的IS显著低于对照组，HCTZ组甚至更低。氯沙坦单用或与HCTZ联合使用均显著增加IS。在所有病例中，IS与肌肉CD相关，但与血浆脂联素或脂质无关。这些结果表明，氯沙坦逆转HCTZ加重的胰岛素抵抗，这可以通过调节葡萄糖代谢受损大鼠的肌肉循环来介导。
The renin–angiotensin system (RAS) is involved in the pathogenesis of insulin sensitivity (IS). The role of RAS in insulin resistance and muscular circulation has yet to be elucidated. Therefore, this study sought to determine the mechanisms of angiotensin II receptor blockers (ARBs) and/or diuretics on IS and capillary density (CD) in fructose-fed rats (FFRs). Sprague-Dawley rats were fed either normal chow (control group) or fructose-rich chow for 8 weeks. For the last 4 weeks, FFRs were allocated to four groups: an FFR group and groups treated with the thiazide diuretic hydrochlorothiazide (HCTZ), with the ARB losartan, or both. IS was evaluated by the euglycemic hyperinsulinemic glucose clamp technique at week 8. In addition, CD in the extensor digitorum longus muscle was evaluated. Blood pressure was significantly higher in the FFRs than in the controls. HCTZ, losartan and their combination significantly lowered blood pressure. IS was significantly lower in the FFR group than in the controls and was even lower in the HCTZ group. Losartan alone or combined with HCTZ significantly increased IS. In all cases, IS was associated with muscular CD, but not with plasma adiponectin or lipids. These results indicate that losartan reverses HCTZ-exacerbated insulin resistance, which can be mediated through the modulation of muscular circulation in rats with impaired glucose metabolism.
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影响因子：
4.9
作者：
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4.9
作者：
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通讯作者：
Ito, Sadayoshi