ENDOTHELIAL DYSFUNCTION IN A MODEL OF HYPERGLYCEMIA AND HYPERINSULINEMIA
ENDOTHELIAL DYSFUNCTION IN A MODEL OF HYPERGLYCEMIA AND HYPERINSULINEMIA
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DOI：
10.1152/ajpheart.1995.269.3.h845
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发表时间：
1995-09-01
影响因子：
4.8
通讯作者：
HAGER, SR
中科院分区：
文献类型：
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作者：
PIEPER, GM;MEIER, DA;HAGER, SR
众所周知，胰岛素缺乏性糖尿病会导致内皮功能障碍。这种功能障碍可能是由高血糖或胰岛素不足引起的。目前尚不清楚当高血糖伴胰岛素水平升高时是否会发生内皮功能障碍。在这项研究中，我们利用高血糖合并高胰岛素血症的实验模型来研究潜在的内皮功能障碍。大鼠连续输注葡萄糖或生理盐水72 h，以达到接近25 mM的峰值血糖浓度。注射葡萄糖的大鼠的血浆胰岛素增加了12倍。72小时后，对照组和葡萄糖灌注组大鼠的血清电解质浓度没有显著差异，血压也没有因此而改变。对照组大鼠的主动脉环对内皮依赖性血管扩张剂乙酰胆碱和A-23187和非内皮依赖性血管扩张剂硝酸甘油均有松弛作用。葡萄糖灌流的大鼠主动脉环对乙酰胆碱的松弛作用减弱，但对A-23187和硝酸甘油的松弛作用不受影响。体外与吲哚美辛或超氧化物歧化酶孵育并不能恢复从葡萄糖灌流的大鼠血管环对乙酰胆碱的受损松弛。因此，高血糖伴高胰岛素血症选择性地损害受体依赖性和内皮依赖性的松弛。这些研究表明，在胰岛素依赖型糖尿病和高血糖诱导的胰岛素抵抗中，高血糖可能是导致内皮功能障碍的常见途径。
Insulinopenic diabetes is known to produce endothelial dysfunction. This dysfunction could arise from either hyperglycemia or inadequate insulin. It is not known whether endothelial dysfunction occurs when hyperglycemia is present with elevated insulin levels. In this study, we utilized an experimental model of hyperglycemia with hyperinsulinemia to investigate latent endothelial dysfunction. Rats were continuously infused with glucose or saline for 72 h to achieve peak plasma glucose concentrations of similar to 25 mM. Plasma insulin rose by 12-fold in glucose-infused rats. No significant differences in serum electrolyte concentration were noted between control and glucose-infused rats after 72 h. Blood pressure was not altered by this intervention. Aortic rings taken from control rats relaxed to the endothelium-dependent vasodilators, acetylcholine and A-23187, and to the endothelium-independent vasodilator, nitroglycerin. Relaxation to acetylcholine but not to A-23187 or nitroglycerin was impaired in glucose-infused rat aortic rings. Incubation in vitro with either indomethacin or superoxide dismutase did not restore the impaired relaxation to acetylcholine in rings taken from glucose-infused rats. Thus hyperglycemia with hyperinsulinemia selectively impairs receptor-dependent, endothelium-dependent relaxation. These studies suggest that elevated glucose may be a common pathway leading to endothelial dysfunction in insulin-dependent diabetes mellitus and hyperglycemia-induced insulin resistance.