替米沙坦对db/db小鼠胰岛分泌功能影响的研究

顾萍 邵加庆 杜宏 卢斌 王扬天 李洁 王燕燕 王坚

·糖尿病基础研究·

基金项目：国家自然科学基金资助项目(30900697，81000352);江苏省自然科学基金资助项目(BK2007574)

作者单位：210002南京军区南京总医院内分泌科

通讯作者：王坚，E-mail: jianwang_11@yahoo.com

【摘要】 目的 探讨替米沙坦阻断肾素-血管紧张素系统(RAS)对db/db小鼠胰岛分泌功能的影响。 方法 将8周龄db/db小鼠随机分为两组，分别给予6周替米沙坦或安慰剂灌胃治疗，同周龄的db/m小鼠作为非糖尿病对照。喂药6周后行糖耐量实验，然后取胰腺，进行胰岛素免疫组化检测，另用离体胰岛灌流系统测定胰岛素第一时相的分泌。 结果 替米沙坦组治疗6周后空腹血糖显著下降(P<0.05)。糖负荷120 min后葡萄糖曲线下面积(AUC)低于安慰剂对照组(P<0.05)，AUCIns0~30高于安慰剂对照组(P<0.05)。离体胰岛灌流 结果 显示，替米沙坦组胰岛素第一时相分泌得到改善。胰岛内胰岛素表达强度替米沙坦组明显高于安慰剂对照组。 结论 替米沙坦能改善糖耐量，恢复胰岛素第一时相分泌，保护β细胞功能。

doi:10.3969/j.issn.1006-6187.2011.06.014

Effects of an angiotensin II type 1 receptor blocker telmisartan on secretory function of β-cell in db/db mice

GU Ping, SHAO Jia-qing, DU Hong, et al. Department of Endocrinology, Nanjing General Hospital of Nanjing Military Command, Nanjing 210002, China

Corresponding author: WANG Jian, E-mail: jianwang_11@yahoo.com

【Abstract】 Objective To investigate whether telmisartan has a protective effect on β-cell function in diabetic state. Methods 8-week-old db/db mice were randomized to telmisartan 5 mg·kg-1·d-1, or placebo group. The age-matched nondiabetic littermates db/m mice were treated with placebo as the controls. After 6 weeks of treatment, intraperitoneal glucose tolerance test and immunohistochemical staining for insulin were performed. Islet perfusion was performed to evaluate kinetics of insulin release by using islet perfusion system. Results Telmisartan provided an improvement of glucose tolerance and greatly rescued islet β-cell mass. Telmisartan treatment also improved first-phase insulin response. Conclusions Telmisartan treatment effectively improves glucose tolerance and β-cell function by significantly restoring first-phase insulin secretion in db/db mice.

【Key words】Telmisartan; Pancreatic islet; Diabetes mellitus, type 2;Renin-angiotensin system