高脂诱发C57BL/6J小鼠Ⅱ型糖尿病模型中胰岛素剪切的变化

摘要

[ Objective ] To establish a high fat induced diabetic mouse model, investigate the possible mechanism under high fat diet effect on insulin processing. [ Method] Establish a type II diabetic mouse model by feeding mouse with high fat diet, determinate the glucose concentration by IPGGT, and the ratio of proinsulin to total insulin by ELTSA under glucose fold. Detect the PCI and PC2 expression level and ER stress related molecular level by Western-blot. [Result] The 10 month age mouse feed with high fat diet demonstrate the diabetes phenotype, after 30 min /60 min /120 min glucose fold, IPGTT results showed that the high fat group mouse blood glucose level was significantjy higher than the control group, but the PCI and PC2 level was lower than control group as detected by Western-blot assay. Meanwhile the ER stress related signal pathway was activated. [Conclusion] The evaluation of high fat feed mouse blood glucose level is probably induced by the block of insulin processing, and the down regulation of PCI and PC2 can be accounted by ER stress signal pathway activation.%[目的]通过建立高脂喂养糖尿病小鼠模型,探究高脂对胰岛素剪切成熟的影响.[方法]通过给C57BL/6J小鼠饲喂高脂饲料建立Ⅱ型糖尿病小鼠模型,通过腹腔葡萄糖耐量试验(IPGTT)法测定高脂糖尿病小鼠血糖浓度,通过酶联接免疫吸附剂测定法检测糖负荷后糖尿病小鼠血液中胰岛素原在总胰岛素中所占的比例,采用Western-blot法检测高脂喂养糖尿病小鼠胰岛中激素原转化酶l(PCl)和激素原转化酶2(PC2)的表达水平及内质网应激(Endoplasmic reticulum stress,ER stress)信号通路相关分子表达.[结果]通过高脂喂养C57B6小鼠,当小鼠达10月龄时,IPGTT检测结果表明糖负荷后30、60、120 min高脂喂养组血糖水平与胰岛素原/总胰岛素均显著高于对照组,Western-blot结果表明,PC1和PC2表达水平均显著降低,其原因可能与ER stress信号通路激活相关.[结论]高脂喂养糖尿病小鼠血糖水平升高可能与PC1和PC2表达水平降低导致的胰岛素剪切障碍有关,PC1和PC2表达水平的降低是由ERstress引起的.