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胰腺局部血管紧张素转化酶相关性羧肽酶与胰岛功能初探

批准号30671001 学科分类材料的设计与制备 ( E030701 )
项目负责人李忠明 负责人职称 依托单位首都医科大学
资助金额0.00
万元
项目类别面上项目 研究期限2007 年 01 月 01 日 至
2009 年 12 月 31 日
中文主题词血管紧张素转化酶2;血管紧张素(1-7);胰岛;糖尿病
英文主题词angiotensin-converting enzyme 2; angiotensin(1-7); islet; diabetes

摘要

中文摘要 新近研究发现肾素-血管紧张素系统(RAS)与胰岛素的合成与释放有关。抑制RAS可以预防糖尿病的发生。新发现的血管紧张素转化酶2(ACE2)是RAS系统的负性调节因子,可以将血管紧张素Ⅱ(AngⅡ)转换为Ang(1-7),后者作用于Mas受体,发挥与AngⅡ相反的作用。ACE2-Ang(1-7)-Mas是传统RAS系统的新途径。我们发现:①ACE2表达于胰岛含胰岛素的β-细胞和含生长抑素的δ-细胞。②用ACE2基因敲除的小鼠与野生型小鼠比较发现,ACE2基因敲除的小鼠第一时相胰岛素分泌缺陷,腹腔葡萄糖耐量试验,糖负荷后的血糖明显增高。而外周组织胰岛素敏感性正常。③应用Ang(1-7)阻断剂-A779,观察正常小鼠血糖、胰岛素水平是否改变,发现其糖耐量试验异常,出现胰岛素抵抗,胰岛细胞凋亡、氧化应激明显增加。④应用Ang(1-7),观察OLETF 2型糖尿病大鼠血糖、胰岛素水平是否改变。发现其糖耐量改善,胰岛素敏感性增加。研究结果从正反两方面表明,ACE2及其酶产物Ang(1-7)对维持正常血糖稳态起保护作用。ACE2-Ang(1-7)-Mas可作为糖尿病预防和治疗的新的药物靶点。
英文摘要 Recent study found that the renin-angiotensin system (RAS) play a role in insulin synthesis and release. RAS inhibition can prevent the occurrence of diabetes. The newly discovered angiotensin-converting enzyme 2 (ACE2) is a negative regulator of RAS system. It can let angiotensin Ⅱ (AngⅡ) convert to Ang (1-7), which act on the Mas receptor and play an opposite effect of AngⅡ. Therefore, ACE2-Ang (1-7)-Mas is a new pass way of the traditional RAS system. We found that: ① ACE2 is expressed in the insulin-containing β-cells and somatostatin-containing δ-cells of the pancreatic islets; ②When compared with wild-type mice, ACE2 gene knockout mice displayed a selective decrease in first-phase insulin secretion in response to glucose intra-abdominal oral glucose tolerance test. While peripheral tissue insulin sensitivity was normal. ③We treated normal glucometabolic mice with Ang(1-7) inhibitor, A779. Peritoneal glucose tolerance test were performed and showed impaired glucose tolerance compared with the controls, as well as increased insulin resistance, islet cell apoptosis and oxidative stress. ④we treated a spontaneous T2D animal model, OLETF rats with Ang(1-7). We found an improvement of glucose tolerance and an increased insulin sensitivity. From the pros and cons, these results suggest that ACE2 and its product, Ang(1-7) can offer protective effects on maintaining glucose homeostasis and support the new pathway of RAS as a potential target for the treatment of T2D.
结题摘要 新近研究发现肾素-血管紧张素系统(RAS)与胰岛素的合成与释放有关。抑制RAS可以预防糖尿病的发生。新发现的血管紧张素转化酶2(ACE2)是RAS系统的负性调节因子,可以将血管紧张素Ⅱ(AngⅡ)转换为Ang(1-7),后者作用于Mas受体,发挥与AngⅡ相反的作用。ACE2-Ang(1-7)-Mas是传统RAS系统的新途径。我们发现:①ACE2表达于胰岛含胰岛素的β-细胞和含生长抑素的δ-细胞。②用ACE2基因敲除的小鼠与野生型小鼠比较发现,ACE2基因敲除的小鼠第一时相胰岛素分泌缺陷,腹腔葡萄糖耐量试验,糖负荷后的血糖明显增高。而外周组织胰岛素敏感性正常。③应用Ang(1-7)阻断剂-A779,观察正常小鼠血糖、胰岛素水平是否改变,发现其糖耐量试验异常,出现胰岛素抵抗,胰岛细胞凋亡、氧化应激明显增加。④应用Ang(1-7),观察OLETF 2型糖尿病大鼠血糖、胰岛素水平是否改变。发现其糖耐量改善,胰岛素敏感性增加。研究结果从正反两方面表明,ACE2及其酶产物Ang(1-7)对维持正常血糖稳态起保护作用。ACE2-Ang(1-7)-Mas可作为糖尿病预防和治疗的新的药物靶点。

成果

序号 标题 类型 作者
1 Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS 期刊 G. Z. Sun|X. L. Zhang|J. C. Chan|M. Y. Yuan|S. Y. Yuan|L. Wang|J. K. Yang|H. J. Fu|G. R. Yang|Y. Feng|X. Xu|X. P. Xu|B. Y. Wu|
2 Improved, Low-Cost Methods for Pancreatic Islet Purification in Rats 期刊 J. K. Yang|G. F. Xue|M. Yu|X. L. Zhang|
3 Meta-analysis of association of ACE2 G8790A polymorphism with Chinese Han essential hypertension 期刊 J. B. Zhou|J. K. Yang|
4 High prevalence of impaired fasting glucose in Chinese children and adolescents with prehypertension/hypertension 期刊 Y. H. Ma|L. Zhao|J. X. Xu|J. K. Yang|S. B. Li|
5 A case-control study on the relationship between HDL2b and non-alcoholic fatty liver disease in Chinese type 2 diabetic patients 期刊 Yang, Jin-Kui|Ma, Ya-Hong|Yang, Dorothy|Zhao, Lei|Konigshofer, Yves|Chang, Elaine|Xian, Xun-De|Van-Cleve, Mark|Wang, Yu-Hui|Huang, Wei|Liu, George|Mueller, Odilo|

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