Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset
Altered action of angiotensin II in patients with type 2 diabetes mellitus of recent onset
复制标题
血管紧张素 II 在新发 2 型糖尿病患者中作用的改变
作者：
D. Fliser;C. Keller;P. Bahrmann;E. Franek;H. Schreckling;K. Bergis;E. Ritz
目的血管紧张素II(Ang II)可增加健康志愿者的胰岛素敏感性。这一效应被认为至少部分是通过骨骼肌血流量的增加来实现的。过去已有文献证明，糖尿病时血管紧张素转换酶II的某些生物学作用发生改变。我们解决了它对胰岛素敏感性的作用是否也是如此的问题。设计与方法将12例健康志愿者(年龄43±9岁)和15例新发2型糖尿病(NIDDM)患者(年龄45±9岁)按随机双盲安慰剂对照设计分为两组，分别给予假静脉滴注和血管紧张素Ⅱ2 ng/(kg·min)静脉滴注。用正糖钳夹技术测定胰岛素刺激的葡萄糖摄取量(M值)，用体积描记法测定小腿肌肉血流量(MBF)，用Dinamap血流仪测定血压，用稳态菊粉(Cin)和对氨基马尿酸(CPAH)清除法测定肾小球滤过率和有效肾血浆流量。结果志愿者静脉注射血管紧张素Ⅱ后的M值(10.1±1.5 mg/kg/min)显著高于对照组(8.2±0.9 mg/kg/min)(P<；0.01)。而糖尿病组血管紧张素Ⅱ水平(6.1±1.3 mg/kg/min)与假输注组(5.5±1.2 mg/kg/min)无显著差异。两组间M值的平均绝对增加值(ΔM)差异有统计学意义(P<；0.02)。正常血糖条件下，糖尿病患者血管紧张素Ⅱ诱导的MBF升高(由15.0±3.5降至15.5±3.9ml/100ml/min，NS)较正常人(16.8±3.3至19.1±3.7ml/100ml/min，P<；0.01)减弱。同样，两组间MBF(ΔMBF)的平均绝对增加之间的差异也是显著的(P<；0.01)。Δ血流量与ΔM显著相关(r=0.6 2，P<0.0 1)。在糖尿病患者和志愿者中，使用血管紧张素转换酶II的平均动脉压绝对急性升高是相似的。Ang II期间的平均Cin、CPAH和钠排出分数显著低于安慰剂组，而肾血管阻力和滤过分数显著高于安慰剂组。这在患者和健康受试者中都可以观察到，但血管紧张素转换酶II对肾脏血流动力学和钠处理的影响在糖尿病患者中更为明显。结论在新发NIDDM患者中，Ang II对胰岛素敏感性和骨骼肌血流的刺激作用减弱。相反，血管紧张素转换酶II对肾脏血流和钠处理的影响在NIDDM患者中比在健康受试者中更明显。
Objective Angiotensin II (Ang II) increases insulin sensitivity in healthy volunteers. This effect is thought to be mediated, at least in part, by an increase in skeletal muscle blood flow. In the past it had been documented that some biological actions of Ang II are altered in diabetes. We addressed the issue of whether this is also true for its action on insulin sensitivity. Design and methods Twelve healthy volunteers (aged 43 ± 9 years) and 15 patients with type 2 diabetes mellitus (NIDDM) of recent onset (aged 45 ± 9 years) were allocated in random order in a double-blind placebo-controlled design to be administered a sham infusion or an infusion of 2 ng Ang II/kg per min. Insulin-stimulated glucose uptake (the M value) was measured with the euglycaemic clamp technique, leg muscle blood flow (MBF) with plethysmography, blood pressure with a Dinamap device, and glomerular filtration rate and effective renal plasma flow with the steady-state inulin (Cin) and p-aminohippurate (CPAH) clearance methods, respectively. Results In volunteers the mean M-value after Ang II infusion (10.1 ± 1.5 mg/kg per min) was significantly higher (P < 0.01) than that after sham infusion (8.2 ± 0.9 mg/kg per min). In contrast, in diabetic patients it was not significantly different with Ang II (6.1 ± 1.3 mg/kg per min) and sham infusion (5.5 ± 1.2 mg/kg per min). The difference in the mean absolute increase in the M value (ΔM) between groups was significant (P < 0.02). The Ang II-induced increase in MBF under euglycaemic conditions was attenuated in diabetic patients (from 15.0 ± 3.5 to 15.5 ± 3.9 ml/100 ml per min, NS) compared with volunteers (from 16.8 ± 3.3 to 19.1 ± 3.7 ml/100 ml per min, P < 0.01). Again, the difference between the mean absolute increases in MBF (ΔMBF) in the groups was significant (P < 0.01). A significant correlation was found between ΔMBF and ΔM (r = 0.62, P < 0.01). The absolute acute increase in mean arterial blood pressure with Ang II was similar in diabetic patients and volunteers. Mean Cin, CPAH and fractional sodium excretion values were significantly lower and renal vascular resistances and filtration fractions higher during the Ang II than they were during the placebo clamp period. This was observed in patients as well as in healthy subjects, but the effects of Ang II on renal haemodynamics and sodium handling were more pronounced in diabetic patients. Conclusions In patients with NIDDM of recent onset the stimulatory effect of Ang II on insulin sensitivity and on skeletal muscle blood flow is attenuated. In contrast, the effects of Ang II on renal perfusion and sodium handling are more pronounced in patients with NIDDM than they are in healthy subjects.
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肾素-血管紧张素系统在正常血压受试者胰岛素敏感性中的作用。
DOI：
10.1097/00000441-199302000-00001
发表时间：
1993
期刊：
The American journal of the medical sciences
影响因子：
--
作者：
Townsend,RR;DiPette,DJ;Lieux,TR;Wolfe,RR
通讯作者：
Wolfe,RR
影响因子：
8.3
作者：
Jamerson, KA;Nesbitt, SD;Julius, S
通讯作者：
Julius, S
影响因子：
15.9
作者：
Steinberg, HO;Chaker, H;Baron, AD
通讯作者：
Baron, AD
血管紧张素 II 的升压剂量可增加血压正常男性中胰岛素介导的葡萄糖摄取。
DOI：
10.1152/ajpendo.1993.265.3.e362
发表时间：
1993
期刊：
The American journal of physiology
影响因子：
--
作者：
Townsend,RR;DiPette,DJ
通讯作者：
DiPette,DJ
影响因子：
15.9
作者：
LAAKSO, M;EDELMAN, SV;BARON, AD
通讯作者：
BARON, AD