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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 observe the effect of exendin-4 (EX-4), a glucagon-like peptide-1 (GLP-1) receptor agonist, on islet α-cells in T2DM rats. Methods T2DM rat model was established by high glucose and high fat diet combined with low dose STZ injection. Male Wistar rats were divided into normal control (NC) group (n = 10), diabetic control group (8) and EX-4 treatment group (EX-4) 8 in the EXL group and 9 in the EX-4 high-dose treatment group. The FPG and glucagon were detected by HE staining to observe the morphological changes. The expression of glucagon was detected by immunohistochemical method. The morphology and quantity of islet α cells were observed. Results After EX-4 intervention for 8 weeks, the levels of glucagon in EXL group and EXH group were significantly lower than those before intervention (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]. The blood glucose of EX-4 group was lower than that of DC group (P <0.01), the percentage of islet α-cells was decreased and the volume of islet was increased compared with DC group. Conclusion EX-4 can reduce the number of pancreatic α-cells in diabetic rats and inhibit the secretion of pancreatic α-cells in rats, thereby improving the blood glucose level in diabetic rats.