THE EFFECT OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITION ON INSULIN ACTION IN HEALTHY-VOLUNTEERS
THE EFFECT OF ANGIOTENSIN-I CONVERTING ENZYME-INHIBITION ON INSULIN ACTION IN HEALTHY-VOLUNTEERS
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DOI：
10.1111/j.1365-2362.1991.tb01405.x
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发表时间：
1991-10-01
影响因子：
5.5
通讯作者：
DONKER, AJM
中科院分区：
文献类型：
--
作者：
GANS, ROB;BILO, HJG;DONKER, AJM
急性高胰岛素血症，达到胰岛素水平在生理范围内，诱导钠潴留。同时，肾素-血管紧张素系统的激活发生，血浆肾素活性（PRA）和血管紧张素- ii水平升高，但血浆醛固酮没有变化。在给予较高药理学剂量的胰岛素后，还可以观察到收缩压和心率的增加，同时注意到PRA和血管紧张素- ii的进一步增加。为了确定血管紧张素-II是否参与观察到的胰岛素作用，我们研究了三种剂量的胰岛素(50 （Ins I), 300 （Ins II）和500 (Ins III) mU kg-1 h-1）在健康受试者接受血管紧张素-I转换酶抑制剂依那普利（10 mg，每天两次）治疗一周后，使用血糖钳技术对肾脏和心血管的影响。对照数据来自先前对同一受试者进行的两项实验，其中一项注射胰岛素，另一项仅注射胰岛素溶剂。胰岛素对钠排泄、血压和心率的影响不受依那普利的影响，这排除了肾素-血管紧张素系统参与胰岛素作用的这些方面。胰岛素敏感性在依那普利治疗期间显著升高(依那普利：Ins I: 11.3 +/- 3.0, Ins II: 20.0 +/- 3.4和Ins III: 20.6 +/- 3.9 mg kg-1 min-1葡萄糖（平均+/- SD）；不含依那普利：Ins I: 8.7 +/- 2.3, Ins II: 13.7 +/- 3.0和Ins III: 15.5 +/- 3.1 mg kg-1 min-1葡萄糖；P < 0.05)。当后一项发现可以在随机研究中得到证实时，依那普利对胰岛素降血糖作用的组织敏感性增强必须被认为是这类药物所有成员的共同特性。
Acute hyperinsulinaemia, achieving insulin levels within the physiological range, induces sodium retention. At the same time an activation of the renin-angiotensin system occurs, with a rise in plasma renin activity (PRA) and angiotensin-II level but no change in plasma aldosterone. After administration of higher, pharmacological doses of insulin an increase in systolic blood pressure and heart rate can also be observed, while further increases in PRA and angiotensin-II are noted. To determine whether angiotensin-II is involved in observed insulin actions, we studied the renal and cardiovascular effects of three dosages of insulin (50 (Ins I), 300 (Ins II) and 500 (Ins III) mU kg-1 h-1) in healthy subjects after one week of treatment with the angiotensin-I converting enzyme inhibitor enalapril (10 mg twice a day), using the euglycaemic clamp technique. Control data were obtained from two previously conducted experiments in the same subjects, one with infusion of insulin and one with the insulin solvent only. The effect of insulin on fractional sodium excretion, blood pressure and heart rate was unaffected by enalapril, which precludes any involvement of the renin-angiotensin system with regard to these aspects of insulin action. Insulin sensitivity increased significantly during treatment with enalapril (with enalapril: Ins I: 11.3 +/- 3.0, Ins II: 20.0 +/- 3.4 and Ins III: 20.6 +/- 3.9 mg kg-1 min-1 glucose (mean +/- SD); without enalapril: Ins I: 8.7 +/- 2.3, Ins II: 13.7 +/- 3.0 and Ins III: 15.5 +/- 3.1 mg kg-1 min-1 glucose; P < 0.05). When this latter finding can be confirmed in a randominized study, enhancement of tissue sensitivity to the glucose-lowering actions of insulin by enalapril must be considered a property common to all members of this class of drugs.