替米沙坦对大鼠胰岛素分泌作用的影响及其机制研究  

The insulinotropic effects and its relevant mechanism of telmisartan in rats

作　　者：崔丽娟[1,2] 杨欢欢 支淋萍 刘涛 CUI Li-juan;YANG Huan-huan;ZHI Lin-ping;LIU Tao(Function Laboratory,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;Dept of Pharmacology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;Dept of General Surgery,Shanxi Bethune Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China)

机构地区：[1]山西医科大学基础医学院机能实验室,山西太原030001 [2]山西医科大学基础医学院药理教研室,山西太原030001 [3]山西白求恩医院,山西医科大学第三医院普通外科,山西太原030032

出　　处：《中国药理学通报》2022年第9期1315-1319,共5页Chinese Pharmacological Bulletin

基　　金：山西省青年科技研究基金资助项目(No 201901D211323);山西省卫健委科研项目(2021148);山西省科技厅基础研究计划资助项目(2021030221224353)。

摘　　要：目的研究替米沙坦对大鼠胰岛素分泌的影响及相关的电生理机制。方法胰岛和胰岛细胞由成年Wistar大鼠胰腺分离获得。通过胰岛素分泌实验观察替米沙坦对胰岛素分泌的影响,使用钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca浓度的影响和对离子通道的作用。结果替米沙坦在低糖浓度下对胰岛素分泌无影响,在高糖浓度下则表现出逐渐增强的促胰岛素分泌作用。钙成像实验显示在高糖浓度下替米沙坦可以升高β细胞内Ca浓度。膜片钳实验表明替米沙坦可以抑制β细胞的电压门控性钾(voltage-gated potassium channel,Kv)通道和激活电压门控性钙通道(voltage-gated calcium channel,VGCC)。结论替米沙坦可以通过作用于β细胞的Kv通道和VGCC升高细胞内Ca浓度,从而葡萄糖浓度依赖性地促进胰岛素分泌。Aim To investigate the insulinotropic effect of telmisartan and the underlying electrophysiological mechanism.Methods Islets and cells were isolated from Wistar rats.Islets were incubated with drugs under different conditions,then supernatant liquid was collected for insulin secretion.Intracellular Ca([Ca])levels ofβ-cells were measured by calcium imaging technology.Patch-clamp technology was applied to detect effects on voltage-gated potassium channel(Kv),and voltage-gated calcium channel(VGCC).Results Not affecting insulin secretion under low glucose condition,telmisartan dose-dependently stimulated insulin secretion under high glucose condition,and stimulation was enhanced with increasing glucose concentration.Acute increases of[Ca]concentration were elicited by telmisartan under high glucose condition.Telmisartan decreased current density of Kv channel,and increased VGCC current density.Conclusions Telmisartan enhanced[Ca]levels ofβ-cells through its action on Kv channel and VGCC,thereby amplifying glucose-stimulated insulin secretion.

关 键 词：替米沙坦 Β细胞 胰岛素分泌 电压门控性钾通道 电压门控性钙通道 全细胞膜片钳 

分 类 号：R-332[医药卫生] R322.57R348.1R347.8R587.1R916.4