Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline‐induced contractility in mesenteric resistance arteries from streptozotocin‐induced diabetic rats
Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline‐induced contractility in mesenteric resistance arteries from streptozotocin‐induced diabetic rats
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通过胰岛素治疗预防内皮功能障碍，但不会增强链脲佐菌素诱导的糖尿病大鼠肠系膜阻力动脉中去甲肾上腺素诱导的收缩力
DOI：
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发表时间：
1994
影响因子：
7.3
通讯作者：
L. Poston
中科院分区：
文献类型：
--
作者：
P. Taylor;B. Oon;C. Thomas;L. Poston
1链脲佐菌素诱导的糖尿病大鼠（Wistar）从糖尿发作时植入缓释胰岛素颗粒（释放速率= 4 u/天）或安慰剂颗粒（棕榈酸）。2在胰岛素治疗（IT）糖尿病动物的肠系膜阻力动脉中评估去甲肾上腺素敏感性、对乙酰胆碱的内皮依赖性舒张和对硝普钠的内皮非依赖性舒张，并与安慰剂植入（PI）糖尿病患者和年龄匹配对照进行比较。3来自PI-糖尿病大鼠的动脉（8-10周）与对照组相比，显示出对去甲肾上腺素的最大反应增强，胰岛素治疗不能阻止这种反应（对照组2.65 ± 0.17 mN mm−1，n = 18支动脉与PI-糖尿病组3.73 ± 0.40 mN mm−1，n = 5，P < 0.05;对照组vs IT-糖尿病组4.02 ± 0.19 mN mm−1，n = 22，P < 0.001）。三组之间对去甲肾上腺素的敏感性相似。4在存在一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（l-NAME）的情况下，IT和PI动脉比对照动脉对去甲肾上腺素更敏感（pEC 50：对照组5.75 ± 0.08，n = 17，与PI-糖尿病组6.14 ± 0.09，n = 8，P < 0.05;对照组与IT-糖尿病组6.38 ± 0.08，n = 20，P < 0.001）。5与对照动脉相比，IT-糖尿病动脉对去极化125 mM K+的最大收缩反应显著增强，但PI-糖尿病动脉无此现象。（最大反应：对照组3.74 ± 0.15 mN mm−1，n = 18，PI-糖尿病组3.61 ± 0.19 mN mm−1，n = 11，NS;对照组vs IT-糖尿病组4.66 ± 0.18 mN mm−1，n = 22，P < 0.001）。6在PI-糖尿病动脉中，乙酰胆碱的内皮依赖性舒张功能严重受损，但在IT-糖尿病动脉中与对照组无显著差异（pEC 50：对照组7.64 ± 0.19，n = 17，vs PI-糖尿病组6.07 ± 0.12，n = 8，P < 0.001;对照组vs IT-糖尿病组7.36 ± 0.09，n = 22，NS）。7在PI-糖尿病动脉中，硝普钠的内皮非依赖性舒张轻微但显著受损，但与对照组相比，IT-糖尿病动脉中无显著差异（pEC 50：对照组7.78 ± 0.10，n = 13，与PI-糖尿病组7.31 ± 0.13，n = 13，P < 0.05;对照组与IT-糖尿病组7.64 ± 0.09，n = 16，NS）。
1 Streptozotocin‐induced diabetic rats (Wistar) were implanted with sustained release insulin pellets (release rate = 4 u day−1) or with placebo pellets (palmitic acid) from the onset of glycosuria. 2 Noradrenaline sensitivity, endothelium‐dependent relaxation to acetylcholine and endothelium‐independent relaxation to sodium nitroprusside were assessed in mesenteric resistance arteries from the insulin‐treated (IT) diabetic animals and compared to placebo‐implanted (PI) diabetics and age‐matched controls. 3 Arteries from PI‐diabetic rats (8–10 weeks) demonstrated an enhanced maximal response to noradrenaline compared to controls, which was not prevented by insulin treatment (control 2.65 ± 0.17 mN mm−1, n = 18 arteries versus PI‐diabetic 3.73 ± 0.40 mN mm−1, n = 5, P < 0.05; control versus IT‐diabetic 4.02 ± 0.19 mN mm−1, n = 22, P < 0.001). Sensitivity to noradrenaline was similar between the three groups. 4 In the presence of the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine methyl ester (l‐NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pEC50: control 5.75 ± 0.08, n = 17, versus PI‐diabetic 6.14 ± 0.09, n = 8, P < 0.05; control versus IT‐diabetic 6.38 ± 0.08, n = 20, P < 0.001). 5 The maximum contractile response to depolarizing 125 mM K+ was significantly enhanced in IT‐diabetic arteries but not PI‐diabetic when compared to control arteries (maximum response: control 3.74 ± 0.15 mN mm−1, n = 18, versus PI‐diabetic 3.61 ± 0.19 mN mm−1, n = 11, NS; control versus IT‐diabetic 4.66 ± 0.18 mN mm−1, n = 22, P < 0.001). 6 Endothelium‐dependent relaxation to acetylcholine was profoundly impaired in the PI‐diabetic arteries, but in the IT‐diabetic arteries was not significantly different from controls (pEC50: control 7.64 ± 0.19, n = 17, versus PI‐diabetic 6.07 ± 0.12, n = 8, P < 0.001; control versus IT‐diabetic 7.36 ± 0.09, n = 22, NS). 7 Endothelium‐independent relaxation to sodium nitroprusside was slightly but significantly impaired in the PI‐diabetic arteries, but was not significantly different in the IT‐diabetic arteries compared to controls (pEC50: control 7.78 ± 0.10, n = 13, versus PI‐diabetic 7.31 ± 0.13, n = 13, P < 0.05; control, versus IT‐diabetic 7.64 ± 0.09, n = 16, NS).
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DOI：
10.1056/nejm198805193182007
发表时间：
1988-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
M. Brownlee;A. Cerami;H. Vlassara
通讯作者：
M. Brownlee;A. Cerami;H. Vlassara
影响因子：
15.9
作者：
HOGAN, M;CERAMI, A;BUCALA, R
通讯作者：
BUCALA, R
影响因子：
158.5
作者：
DETEJADA, IS;GOLDSTEIN, I;COHEN, RA
通讯作者：
COHEN, RA
胰岛素可减弱大鼠血管平滑肌细胞中加压素诱导的钙瞬变和电压依赖性钙反应。
DOI：
10.1172/jci115426
发表时间：
1991
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Standley,PR;Zhang,F;Ram,JL;Zemel,MB;Sowers,JR
通讯作者：
Sowers,JR
影响因子：
158.5
作者：
MAKITA, Z;RADOFF, S;VLASSARA, H
通讯作者：
VLASSARA, H