Department of Endocrinology, Union Hospital, Tongji Medical College of HuaZhong, University of Science & Technology, Wuhan 430022, China.
J Diabetes Res. 2013;2013:405284. doi: 10.1155/2013/405284. Epub 2013 Mar 19.
The aim of this study was to evaluate the effects of angiotensin-converting enzyme 2 (ACE2) on glucose homeostasis and islet function in mice. Male wildtype (WT) and ACE2 knockout (ACE2 KO) mice were divided into chow diet group and long-term high-fat diet (HFD) group. After 16 weeks of feeding, the islet function of the animals was evaluated by intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin releasing test (IPIRT). The pancreas was immunohistochemically stained to analyze the relative content of insulin (IRC), vascular endothelial growth factor (VEGF), and microvessel density (MVD) in islets. There was no difference of body weight, area under curve of glucose (AUCG), area under curve of insulin from 0 to 5 min (AUGI0-5), MVD, and RVC (relative content of VEGF) between WT and ACE2 KO mice with regular chow diet. Under the condition of long-term HFD, the AUCG of ACE2 KO mice was increased obviously in comparison with the WT mice, with decreased IRC, MVD, AUGI0-5, AUCI0-30, and RVC (all P < 0.05). In conclusion, these results show that ACE2 deficiency deteriorates islet function of mice with long-term HFD via impairment of islet microvasculature.
本研究旨在评估血管紧张素转换酶 2（ACE2）对小鼠葡萄糖稳态和胰岛功能的影响。雄性野生型（WT）和 ACE2 敲除（ACE2 KO）小鼠分为普通饲料组和长期高脂肪饮食（HFD）组。喂养 16 周后，通过腹腔葡萄糖耐量试验（IPGTT）和腹腔胰岛素释放试验（IPIRT）评估动物的胰岛功能。对胰腺进行免疫组织化学染色，分析胰岛中胰岛素（IRC）、血管内皮生长因子（VEGF）和微血管密度（MVD）的相对含量。在常规饲料喂养下，WT 和 ACE2 KO 小鼠的体重、血糖曲线下面积（AUCG）、0 至 5 分钟胰岛素曲线下面积（AUGI0-5）、MVD 和 RVC（VEGF 的相对含量）均无差异。在长期 HFD 条件下，ACE2 KO 小鼠的 AUCG 明显高于 WT 小鼠，IRC、MVD、AUGI0-5、AUCI0-30 和 RVC 降低（均 P < 0.05）。综上所述，这些结果表明 ACE2 缺乏通过损害胰岛微血管导致长期 HFD 小鼠的胰岛功能恶化。
