Avandamet对糖尿病小型猪胰岛β细胞及糖代谢的影响

Effect of Avandamet on islet β cells in diabetic miniature pigs

目的:研究复方制剂二甲双胍马来酸罗格列酮(Avandamet)对糖尿病小型猪胰岛β细胞及糖代谢的影响。方法:将贵州小型猪15头随机分为3组:正常组喂普通猪饲料;模型组喂高脂高蔗糖饲料;治疗组前3个月喂高脂高蔗糖饲料,从第4个月开始,在高脂高蔗糖饲料中加Avandamet,4mg/次,2次/d。每月末从眶静脉窦采集空腹血样,氧化酶法测定血糖,用放射免疫分析法测定血浆胰岛素、TNF-α水平。第6个月和第8个月末各进行1次口服葡萄糖耐量试验(OGTT)。第6个月末进行胰岛素敏感性试验,计算胰岛素敏感性指数(Ki)。第8个月末处死动物,取胰腺标本,测定胰腺组织中胰岛素含量。用HE染色和免疫组织化学染色方法观察胰岛β细胞在胰岛中所占面积的百分比。结果:OGTT中,正常组血糖水平在口服葡萄糖后30min时达最高水平,后逐渐下降至正常;模型组血糖水平在口服葡萄糖后90min时才达最高水平;模型组动物空腹血糖、血胰岛素、血TNF-α水平较正常组升高(P<0.05);模型组Ki值较正常组减小(P<0.05)。治疗组动物空腹血糖、血胰岛素、血TNF-α水平较模型组降低(P<0.05);葡萄糖耐量与正常组相似;Ki值较模型组升高(P<0.05),与正常组持平;胰腺组织结构基本正常,较模型组明显改善,胰腺组织中胰岛素含量、胰岛β细胞占胰岛面积的百分比均较模型组升高(P<0.05)。结论:复方制剂Avandamet有降低糖尿病小型猪血浆葡萄糖水平,减轻胰岛素抵抗和保护胰岛β细胞的作用。

Aim ： To study the effect of Avandamet on islet β cells in diabetic miniature pigs and its mechanism of adjusting glucose metabolism. Mothods：Fifleen Guizhou miniature pigs were randomly divided into 3 groups： normal control group （ control diet） , experiment group （ high fat/high sucrose diet） , treatment group （ high fat high sucrose plus treatment by Avandamet）. At the end of each month, the fasting blood samples were collected from the orbital sinus of the animals and the concentrations of blood glucose and insulin were detected. Oral glucose tolerance test （OGTT） and insulin sensitivity test were performed at the end of month 6. At the end of month 8, the animals were sacrificed and the pancreatic tissues were dissected from each animal. The insulin concentrations of pancreatic tissues were defected. The structure changes of pancreatic islet β cells were observed by HE staining and immunohistochemistry. Results ： The levels of glucose and insulin in plasma increased significantly in experiment group （P 〈 0.01 ） and this diet also induced insulin resistance and impairment of pancreatic islet β cells. The concentration of fasting plasma glucose was decreased significantly in treatment group （P 〈0.01 ）. The clearance of plasma glucose and the acute phase of insulin secretion were obviously improved and the structure and function of pancreatic islet β cells were protected in treatment group. Conclusion ： Avandamet has the roles of reducing plasma glucose, alleviating insulin resistance and protecting pancreatic islet β cells in diabetic miniature pigs.