1型糖尿病小鼠胰岛β细胞量的变化及其机制

The change of β cell mass and its mechanism in type 1 diabetic mice

目的研究1型糖尿病(T1DM)小鼠胰岛β细胞量的变化及变化机制。方法糖尿病第4、12、20周时,T1DM小鼠被放血处死。以Insulin、Kruppel-like factor 4(KLF4)、Caspase-3、TUNEL的免疫荧光标记及再生蛋白1 mRNA半定量RT-PCR检测β细胞量、β细胞再生和凋亡。结果β细胞量随糖尿病发病时间延长逐渐减少,至糖尿病第12周时降至最低,第20周与第12周比较无统计学差异。β细胞量的变化与其Caspase-3、KLF4的表达和胰腺再生蛋白1 mRNA的丰度密切相关。结论 1型糖尿病鼠胰岛β细胞并未完全丧失,其机制与β细胞凋亡减少、再生增加密切相关。

Objective To explore the change of β cell mass and its mechanism in type 1 diabetic mice. Methods Type 1 diabetic mice were killed by exsanguination after 4, 12 and 20 weeks of diabetes, respectively. Indirect irnmunofluorescences for insulin, Kruppel like factor 4 （KLF4）, caspase-3 and TUNEL and semi-quantitative RT-PCR for pancreatic regenerating protein 1 mRNA were used to evaluate pancreatic β cell mass, β cell regeneration and apoptosis. Results The β cell mass was gradually decreased in diabetic mice along with time until 12-week of diabetes. No significant difference in β cell mass between 12-week and 20-week of diabetic course was demonstrated. Such change of β cell mass was associated with the variances of caspase-3, KLF4 in β ceils and the regenerating protein 1 mRNA expression in pancreata. Conclusion The β cell mass is not totally lost in type 1 diabetic mice which seems to be strongly associated with attenuated β cell apoptosis and with improved β cell neogenesis.