胰升血糖素样肽-1受体激动剂对糖尿病大鼠胰岛α细胞功能影响的研究

Effects of glucagon-like peptide-1 receptor agonists on the isletαcell function in type 2 diabetic rats

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,将EX-4组进一步分为EX-4低剂量治疗(EXL)组8只,EX-4高剂量治疗(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[(388.00±27.19)vs(300.40±8.92)pg/ml,(364.20±19.54)vs(241.20±26.48)pg/ml,P<0.05],EX-4组血糖较DC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可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。

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 αcells . 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 [（388.00 ± 27.19 ） vs （300.40 ± 8.92）pg/ml ,（364.20 ± 19.54） vs （241.20 ± 26.48）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 αcells ,thereby improves the glucose status in diabetic rats .