Gender Differences in Endothelial Function in Aortas From Type 2 Diabetic Model Mice
Gender Differences in Endothelial Function in Aortas From Type 2 Diabetic Model Mice
复制标题
DOI：
10.1254/jphs.09133fp
复制
发表时间：
2009-09-01
影响因子：
3.5
通讯作者：
Kamata, Katsuo
中科院分区：
文献类型：
--
作者：
Takenouchi, Yasuhiro;Kobayashi, Tsuneo;Kamata, Katsuo
2型糖尿病与高死亡率和发病率相关，主要是由于冠状动脉疾病和动脉粥样硬化，尽管女性是例如动脉粥样硬化和高血压发展的保护因素。我们的主要目的是研究2型糖尿病模型小鼠血管内皮功能的性别差异。糖尿病小鼠（雄性和雌性）的非空腹血糖水平显著升高。对照组和糖尿病患者（无论性别）之间的血浆胰岛素水平没有差异。糖尿病患者血浆脂联素水平降低，男性更低。在对照组（来自男性或女性）中，可乐定诱导的舒张被Akt抑制剂处理废除。糖尿病男性（与对照雄性和糖尿病雌性相比）：a）可乐定和胰岛素诱导的内皮依赖性主动脉舒张功能受损，而乙酰胆碱（ACh）和硝普钠（SNP）诱导的主动脉舒张功能未受损，B）去甲肾上腺素（NE）诱导的主动脉收缩反应增强，c）全身血压升高，和d）主动脉中可乐定刺激的Akt的Ser-473磷酸化降低。这些结果表明，依赖于Akt通路的内皮功能仅在雄性小鼠中被2型糖尿病废除。
Type 2 diabetes mellitus is associated with high mortality and morbidity, mainly due to coronary artery disease and atherosclerosis, although female gender is a protective factor in the development of, for example, atherosclerosis and hypertension. Our main aim was to investigate gender differences in endothelial function in aortas from type 2 diabetic model mice. The nonfasting plasma glucose level was significantly elevated in diabetic mice (both males and females). The plasma insulin level was not different between controls and diabetics (either gender). The plasma adiponectin level was decreased by diabetes, and was lower in males. In control aortas (from males or females), the clonidine-induced relaxation was abolished by Akt-inhibitor treatment. In diabetic males (versus both control males and diabetic females): a) the clonidine- and insulin-induced endothelium-dependent aortic relaxations were impaired, but the acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced aortic relaxations were not, b) the norepinephrine (NE)-induced aortic contractile response was enhanced, c) systemic blood pressure was elevated, and d) the clonidine-stimulated Ser-473 phosphorylation of Akt in the aorta was decreased. These results suggest that endothelial functions dependent on the Akt pathway are abrogated by type 2 diabetes only in male mice.