胰高糖素样肽-1受体激动剂对糖耐量受损大鼠胰岛α细胞结构与功能的影响  

Effect of glucagon-like peptide 1 receptor agonists on the structure and function of pancreatic alpha cells in rats with impaired glucose tolerance

作　　者：郗光霞[1] 任伟[1] 赵凌霞[1] 范雪梅[1] 杨坤[1] 梁登耀 冯瑜 Xi Guangxia;Ren Wei;Zhao Lingxia;Fan Xuemei;Yang Kun;Liang Dengyao;Feng Yu(Department of Endocrinology,Shanxi Academy of Medical Sciences Shanxi Dayi Hospital,Taiyuan 030032,China)

机构地区：[1]山西医学科学院山西大医院内分泌科,太原030032

出　　处：《中华糖尿病杂志》2019年第10期677-684,共8页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：山西省自然科学基金 (2013011048-3)。

摘　　要：目的观察胰高糖素样肽-1(GLP-1)受体激动剂艾塞那肽(exendin-4)对糖耐量受损(IGT)大鼠胰岛α细胞结构与功能的影响。方法选用4~5周龄(150~170 g)清洁级雄性Wistar大鼠54只,采用随机数字表法分为糖耐量正常组(NGT组,n=18)和糖耐量受损组(n=36)。NGT组给予常规饲料,糖耐量受损组给予高糖脂饲料建立IGT大鼠模型32只,造模成功率88%,将成模糖耐量受损大鼠随机分为糖耐量受损对照组(IGT组,n=16)和Exendin-4干预组(Ex组,n=16)。3组各取1/2数量大鼠采用放射免疫法测血清胰高糖素水平;免疫组化染色、免疫荧光单标法测α细胞面积及胰高糖素蛋白水平;电镜观察α细胞超微结构。另Ex组大鼠予Exendin-45μg/kg腹部皮下注射,NGT、IGT组予生理盐水5μg/kg皮下注射。4周后复测上述各指标。各组间比较采用单因素方差分析和最小显著性差异法t检验。结果(1)干预前,与NGT组比较,IGT及Ex组大鼠血清胰高糖素水平升高,分别为(118.89±3.53)、(116.12±3.37)比(88.18±6.94)pg/ml,α细胞面积占比(26.91±7.77)%、(24.00±9.88)%比(11.01±6.33)%、胰高糖素蛋白表达水平(307.44±71.85)、(321.71±105.65)比(71.74±12.10),分泌颗粒数(135.32±16.31),(129.64±12.78)比(74.60±6.55)个(均P<0.05)。与干预前及同期IGT组相比,Ex组干预后血清胰高糖素(86.89±6.23)比(116.12±3.37)、(118.39±4.36)pg/ml(t=11.67、11.72,均P<0.05)、α细胞面积占比(15.09±3.35)%比(24.00±9.88)%,(29.21±5.66)%、胰高糖素蛋白表达水平(102.10±26.28)比(321.71±105.65)、(327.55±155.53),分泌颗粒数(75.79±8.23)比(129.64±12.78)、(133.39±4.36)个(t=10.02、17.49,均P<0.05)。与同期NGT组比较,Ex组干预后上述指标差异无统计学意义(均P>0.05);(2)电镜下超微结构变化显示,与NGT组比较,IGT组α细胞核膜皱缩,核染色质固缩;线粒体及内质网排列不规则,线粒体肿胀变形、嵴变短浅;内质网基粒脱落;分泌颗粒增多,致密芯与界膜间隙变窄甚至消�Objective To investigate the effect of glucagon-like peptide(GLP)-1 receptor agonist(exendin-4)on the structure and function of pancreaticαcells in impaired glucose tolerance(IGT)rats.Methods A total of 54 male Wistar rats aged 4-5 weeks(150-170 g)were randomly divided into normal glucose tolerance(NGT)group(n=18)and IGT group(n=36).Rats in NGT group were administrated with routine diet and rats in IGT group were administrated with high-sugar,high-fat diet.32 rats which were successfully established IGT models(the modeling success rate was 88%)were randomly divided into the IGT group(IGT group,n=16)and the Exendin-4 intervention group(Ex group,n=16).Levels of plasma glucagon,the percentage ofαcells area and the glucagon protein expression in half rats of each group were detected by radioimmunoassay,immunohistochemical staining and immunofluorescence respectively.The ultrastructure ofαcells were observed under transmission electron microscope.Rats in Ex group received Exendin-45μg/kg subcutaneously,twice daily,while rats in the NGT and IGT group both received saline 5μg/kg instead.Indicators were detected and collected after intervention for 4 weeks.One-way analysis of variance and least-significant difference was used for multigroup comparison.Results(1)Before intervention,the plasma levels of glucagon,the area percentage ofαcells,the glucagon protein expression and the secretory granules level ofαcells in IGT group and Ex group were higher than those in the NGT group respectively[glucagon:(118.89±3.53),(116.12±3.37)vs(88.18±6.94)pg/ml;the area percentage ofαcells:(26.91±7.77)%,(24.00±9.88)%vs(11.01±6.33)%;the glucagon protein expression:(307.44±71.85),(321.71±105.65)vs(71.74±12.10);the secretory granules level ofαcells:(135.32±16.31),(129.64±12.78)vs(74.60±6.55);all P<0.05).After intervention,the plasma levels of glucagon,the area percentage ofαcells,the glucagon protein expression and the secretory granules levels of rat isletαcells were less in Ex group than those in the IGT group and th

关 键 词：胰高血糖素样肽-1 胰高血糖素 超微结构 糖耐量受损 Α细胞 

分 类 号：R58[医药卫生—内分泌]