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Mibefradil抑制高糖诱导的胰岛素分泌作用及其机制的初步研究

, PP. 660-665

Keywords: Mibefradil,胰岛细胞,胰岛素分泌,糖尿病

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Abstract:

目的初步探讨Mibefradil对高糖作用下胰岛细胞胰岛素分泌的作用及其机制。方法体外培养大鼠胰岛瘤β细胞株(INS-1),将INS-1细胞分为对照组(11.1mmol/L葡萄糖)、高糖组(33.3mmol/L葡萄糖)、药物组(11.1mmol/L葡萄糖+1μmol/LMibefradil、1μmol/LNNC55-0396、10μmol/L尼卡地平)、高糖+药物组(33.3mmol/L葡萄糖+1μmol/LMibefradil、1μmol/LNNC55-0396、10μmol/L尼卡地平),先用不同浓度葡萄糖孵育细胞48h,再按分组加入药物继续孵育24h。采用放射免疫法检测细胞培养上清胰岛素含量,RT-PCR及Westernblot检测T型钙通道cav3.1、cav3.2亚基表达。结果与对照组相比,高糖组能够明显增加细胞胰岛素分泌(P<0.05)和胰岛细胞T型钙通道cav3.1、cav3.2基因及蛋白表达(P<0.05),而药物组胰岛细胞胰岛素分泌水平和T型钙通道cav3.1、cav3.2亚基基因及蛋白表达则与对照组无显著差异(P>0.05);与高糖组相比,高糖+药物组可不同程度降低INS-1细胞胰岛素分泌,其中Mibefradil组显著降低胰岛素分泌(P<0.05)和T型钙通道cav3.1、cav3.2亚基基因及蛋白表达(P<0.05)。结论Mibefradil可能通过下调胰岛细胞T型钙通道cav3.1、cav3.2亚基表达抑制高糖作用下INS-1细胞胰岛素分泌。

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