糖尿病基础研究

　　【摘要】目的 观察胰升血糖素样肽-1(GLP-1)受体激动剂Exendin-4(EX-4)对T2DM大鼠胰岛α细胞的影响。 方法 高糖高脂喂养联合小剂量STZ注射建立T2DM大鼠模型。将雄性Wistar大鼠随机分为正常对照(NC)组10只、糖尿病对照(DC)组8只和EX-4治疗 (EX-4) 组17只，其中，EX-4低剂量(EXL)组8只，EX-4高剂量(EXH)组9只。检测FPG、胰升血糖素，HE染色观察形态学变化，免疫组织化学法检测胰升血糖素表达水平，观察胰岛α细胞形态及数量。 结果 EX-4干预8周后，EXL组和EXH组胰升血糖素水平较干预前下降[(300.40±8.92) vs (388.00±27.19)pg/ml，(241.20±26.48) vs (364.20±19.54)pg/ml，P<0.05]，EX-4组血糖较DM组下降(P<0.01)，胰岛α细胞百分比较DC组减少，胰岛体积较DC组增大。 结论 EX-4减少糖尿病大鼠胰岛α细胞数量，抑制大鼠胰岛α细胞分泌功能，从而改善糖尿病大鼠血糖水平。

　　【关键词】Exendin-4;糖尿病;胰升糖素样肽-1受体激动剂;胰升血糖素;胰岛α细胞

　　【Abstract】 Objective To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on the pancreatic islet α cells of T2DM rats. Methods A total of 40 male Wistar rats were randomly divided into the normal control (NC) group (n=10) and the diabetic model group (n=30). T2DM rat models were established by being fed with sucrose and fat-enriched diet and then by intraperitoneal injection of 1% STZ 35 mg/kg. The 25 alive rats in the model group were randomly divided into diabetic control (DC, n=8) group and the exendin-4 intervention (EX-4, n=17) group, including low dose of EX-4 (EXL, n=8) group, high dose of EX-4 (EXH, n=9) group. All rats were sacrificed after exendin-4 treatment for eight weeks. The levels of FPG were measured. Serum glucagon levels were measured by radioimmunoassay. Pancreas HE staining was adopted to determine the morphological changes. Immunohistochemical method was used to analyze the expression of glucagon in α cells. Results Compared to DC group, the blood glucose levels in EX group decreased significantly. After exendin-4 treatment for eight weeks, the serum glucagon levels decreased significantly [(300.40±8.92) vs (388.00±27.19)pg/ml,(241.20±26.48) vs (364.20±19.54)pg/ml, P<0.05]. There was a reduction of the percentage of pancreatic islet α cells and an increase of islets volume in EX group than those in DC group. Conclusion Exendin-4 reduces the number of pancreatic islet α cells, inhibit the secretion function of α cells, thereby improves the glucose status in diabetic rats.

　　【Key words】Exendin-4;Diabetes mellitus;Glucagon-like peptide-1 (GLP-1) receptor agonists;Glucagon;Islet α cell