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血管紧张素转换酶抑制剂改善胰岛素敏感性的作用机制。

The mechanisms of insulin sensitivity improving effects of angiotensin converting enzyme inhibitor.

作者信息

Ura N, Higashiura K, Shimamoto K

机构信息

The Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, Japan.

出版信息

Immunopharmacology. 1999 Oct 15;44(1-2):153-9. doi: 10.1016/s0162-3109(99)00087-9.

Abstract

It is well-known that angiotensin converting enzyme (ACE) inhibitor not only decreases blood pressure (BP) but also improves insulin sensitivity. To elucidate the mechanisms of these actions of ACE inhibitor, we evaluated its effect on both BP and insulin sensitivity (M-value) as estimated by the glucose clamp technique in essential hypertensives in comparison with the effect of angiotensin receptor (AT) antagonist. We also evaluated the effect of ACE inhibitor on BP, M-value and muscle fiber composition in fructose-fed rats (FFR) as an insulin-resistant hypertensive model with or without treatment with Hoe 140 (kinin receptor antagonist). In essential hypertensives, both ACE inhibitor and AT antagonist decreased BP and improved insulin sensitivity to the same extent. In FFR, ACE inhibitor also decreased BP and improved insulin sensitivity. Moreover, Hoe 140 showed no effect on these actions of ACE inhibitor. The composite ratio of type I fiber of soleus muscle was decreased significantly in FFR compared to control and ACE inhibitor produced a recovery of the composite ratio of type I fiber to the same as control. These results suggested that muscle fiber composition of skeletal muscle is linked to insulin resistance, and that ACE inhibitor may modulate muscle fiber composition through its vasodilative effect in hypertension. These results also suggest that for vasodilation, it is more important to inhibit angiotensin II than to block degradation of kinins or to improve insulin sensitivity by ACE inhibitor.

摘要

众所周知,血管紧张素转换酶(ACE)抑制剂不仅能降低血压(BP),还能改善胰岛素敏感性。为了阐明ACE抑制剂这些作用的机制,我们通过葡萄糖钳夹技术评估了其对原发性高血压患者血压和胰岛素敏感性(M值)的影响,并与血管紧张素受体(AT)拮抗剂的作用进行了比较。我们还评估了ACE抑制剂对果糖喂养大鼠(FFR)的血压、M值和肌肉纤维组成的影响,FFR是一种胰岛素抵抗性高血压模型,分别给予或不给予Hoe 140(激肽受体拮抗剂)治疗。在原发性高血压患者中,ACE抑制剂和AT拮抗剂均能同等程度地降低血压并改善胰岛素敏感性。在FFR中,ACE抑制剂也能降低血压并改善胰岛素敏感性。此外,Hoe 140对ACE抑制剂的这些作用没有影响。与对照组相比,FFR中比目鱼肌I型纤维的复合比例显著降低,而ACE抑制剂可使I型纤维的复合比例恢复至与对照组相同。这些结果表明,骨骼肌的肌肉纤维组成与胰岛素抵抗有关,ACE抑制剂可能通过其在高血压中的血管舒张作用来调节肌肉纤维组成。这些结果还表明,对于血管舒张而言,抑制血管紧张素II比阻断激肽降解或通过ACE抑制剂改善胰岛素敏感性更为重要。

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