摘要
目的一些大规模流行病学研究显示血管紧张素(angiotension,Ang)Ⅱ受体拮抗剂能减少2型糖尿病的发生,但其机制尚未阐明。文中旨在探讨替米沙坦(Telmisartan)体外干预对小鼠体外胰岛的第一相胰岛素分泌功能的影响。方法 18只8周龄db/m非糖尿病小鼠,随机分为3组,每组6只,编为A、B、C组。另12只db/db糖尿病小鼠随机分为2组,每组6只,编为D、E组。分离胰岛后,A^E组分别给予含有空白、100 nmol/LAngⅡ、10μmol/L替米沙坦+100 nmol/LAngⅡ、空白、10μmol/L替米沙坦的培养液孵育及灌流。收集高糖灌流后0~30 min各时间点的灌出液,测定胰岛素水平。结果 AngⅡ孵育灌流的db/m小鼠胰岛的胰岛素第一相分泌显著下降,仅达到基础水平的4倍,而预先给予替米沙坦后,AngⅡ孵育灌流的db/m小鼠胰岛的胰岛素第一相分泌明显改善,达到基础水平的7倍左右。db/db小鼠体外胰岛的胰岛素分泌在高糖刺激后胰岛素第一相分泌明显受损,小于基础值的2倍,仅为3μg/L。而替米沙坦孵育灌流的db/db小鼠胰岛的胰岛素分泌在给予16.7 mmol/L葡萄糖后1 min即达到最高值6μg/L,显示胰岛素第一相分泌明显改善。结论替米沙坦体外干预阻断局部肾素血管紧张素系统(renin angiotensin system,RAS)活性,显著改善了胰岛β细胞第一时相分泌,保护胰岛功能,这可能是阻断RAS降低糖尿病发病率的保护机制之一。
Objective Some epidemiological studies suggest that the angiotensin Ⅱ（AngⅡ） type 1 receptor blocker reduces the risk of developing type 2 diabetes.Yet its mechanisms remain to be elucidated.The aim of this study was to explore the effects of telmisartan on the first-phase insulin secretion of islets in vitro in db/db mice.Methods Eighteen db/misty mice,8 weeks of age,were equally randomized to groups A,B and C,and another 12 age-matched db/db mice to groups D and E.After isolation,the islets of groups A-E were incubated and perfused with media containing blank,100 nmol /L AngⅡ,10 μmol/L telmisartan ＋100 nmol /L AngⅡ,blank,and 10 μmol/L telmisartan,respectively.Samples were collected at different time points between 0 and 30 min after 16.7 mmol/L glucose perfusion for the measurement of insulin levels.Results The first-phase insulin secretion of the db/misty mice was significantly impaired by AngⅡ,its peak only 4 times the height of the basal level,but markedly improved by telmisartan pretreatment,its peak 7 times as high as the basal level.The first-phase insulin secretion of the db/db mice was decreased to less than 3 μg/L,but increased to 6 μg/L at 1 min after administration of 16.7 mmol/L glucose.Conclusion By blocking the local rennin angiotensin system（RAS）,telmisartan intervention can remarkably improve the first-phase insulin secretion of islets in vitro in db/db mice,and thus protect the β-cell function,which may be involved in the mechanisms of its anti-diabetic benefits.
出处
《医学研究生学报》
CAS
2010年第9期900-903,共4页
Journal of Medical Postgraduates
基金
国家自然科学基金(30900697)
江苏省自然科学基金(BK2007574)
江苏省"六大人才高峰"高层次人才培养对象C类资助
关键词
糖尿病
胰岛
第一相胰岛素分泌
替米沙坦
Diabetes
Pancreatic islet
First-phase insulin secretion
Telmisartan
