Hyperglycemia and hyperlipidemia are associated with endothelial dysfunction during the development of type 2 diabetes
Hyperglycemia and hyperlipidemia are associated with endothelial dysfunction during the development of type 2 diabetes
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DOI：
10.1139/y07-026
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发表时间：
2007-05-01
影响因子：
2.1
通讯作者：
van Breemen, Cornelis
中科院分区：
文献类型：
--
作者：
Okon, Elena B.;Chung, Ada W. Y.;van Breemen, Cornelis
糖尿病损害内皮功能，这可以被认为是心血管疾病发展的标志。高血糖、高胰岛素血症和高脂血症被认为导致内皮功能障碍。在本研究中，我们在小鼠模型中研究了 2 型糖尿病发展过程中这些血浆代谢标志物与内皮功能之间的可能联系。使用8周、12周和16周时的C57BL/6J-Lep(ob/ob)小鼠来研究2型糖尿病建立过程中的内皮功能。通过测量乙酰胆碱（ACh）刺激的血管舒张，在体外评估胸主动脉的内皮功能。获取血浆用于测量葡萄糖、胰岛素、甘油三酯和胆固醇水平。相关性和多元回归分析显示，8 周龄时乙酰胆碱反应性与血浆葡萄糖、胰岛素和血脂水平之间存在很强的负相关性。在老年小鼠和 C57BL/6J 小鼠中均未观察到这种关联。总之，血浆葡萄糖、胰岛素和脂质水平的升高与2型糖尿病发展早期的内皮功能受损有关。年龄较大时相关性的丧失表明疾病后期内皮功能和心血管并发症的多因素调节。
Diabetes mellitus impairs endothelial function, which can be considered as the hallmark in the development of cardiovascular diseases. Hyperglycemia, hyperinsulinemia, and hyperlipidemia are believed to contribute to endothelial dysfunction. In the present study, we investigated the possible links among these plasma metabolic markers and endothelial function in a mouse model during the development of type 2 diabetes. C57BL/6J-Lep(ob/ob) mice at 8, 12, and 16 weeks were used to study endothelial function during the establishment of type 2 diabetes. Endothelial function was accessed in vitro in the thoracic aorta by measuring acetylcholine (ACh)-stimulated vasodilatation. Blood plasma was obtained for the measurements of glucose, insulin, triglycerides, and cholesterol levels. Correlation and multiple regression analysis revealed strong negative associations between the ACh responsiveness and the plasma levels of glucose, insulin, and lipid profiles at the age of 8 weeks. Associations were observed at neither older age nor in C57BL/6J mice. In conclusion, the increase in plasma levels of glucose, insulin, and lipids is associated with the impairment of the endothelial function during the early stage of the development of type 2 diabetes. The loss of correlation at an older age suggests multifactorial regulation of endothelial function and cardiovascular complications at later stages of the disease.