血脂康通过葡萄糖感受器影响db/db小鼠胰岛r分泌功能的研究

摘要

目的 探讨血脂康对db/db小鼠胰岛内葡萄糖转运蛋白-2(GLUT-2)和葡萄糖激酶(GCK)表达的影响.方法 将40只8周龄清洁级雄性C57BL/KsJ-db/db小鼠随机分为血脂康组和db/db组,每组20只,分别给予300 mg/(kg·d)血脂康和等剂量安慰剂(0.5%纤维素钠)灌胃;选取20只同周龄同窝C57BL/KsJ-db/m小鼠作为非糖尿病对照组(db/m组),给予安慰剂灌胃.各组小鼠均连续灌胃8周后行腹腔葡萄糖耐量试验,以离体胰岛灌流法评价胰岛分泌功能,分别采用qRT-PCR和Western blot方法检测胰岛β细胞葡萄糖感受器GLUT-2和GCK mRNA及蛋白表达水平.结果 在糖负荷后306,0,120 min,血脂康组血糖水平均明显低于db/db组(P均<0.05),但均高于db/m组(P均<0.05);在糖负荷后30 min,血脂康组血浆胰岛素水平明显高于db/db组(P<0.05).与db/db组比较,血脂康组在2.8 mmol/L低糖灌流时胰岛素分泌无明显升高,而给予16.7 mmol/L高糖刺激1 min后胰岛素分泌明显升高(P<0.05),但仍低于db/m组(P<0.05).db/db组GLUT-2和GCK mRNA及蛋白表达水平均明显低于db/m组(P均<0.05),血脂康组GLUT-2和GCK mRNA及蛋白表达水平均明显高于db/db组(P均<0.05).结论 血脂康能通过增加胰岛β细胞GLUT-2和GCK的表达改善胰岛分泌功能.%Objetcive It is to investigate the effects of Xuezhikang on pancreatic islet endocrine function and local GLUT -2 and GCK expression levels in db/db mice.Methods A total of 40 male genetically diabetic C57BL/KsJ-db/db mice were randomly divided into two groups with 20 cases in each.These animals were treated with Xuezhikang at 300 mg/(kg· d) in Xuezhikang group or equal dose placebo of 0.5%cellulose sodium in db/db group for intragastric administration .In addition, another 20 cases of aged-matched lean non-diabetic C57BL/KsJ-db/m littermates served as a wild-type control for db/m group were treated with equal dose placebo. After 8-week treatment , 10 mice were randomly selected from each group and received intraperitoneal glucose tolerance test ( IPGTT) .And the in vitro insulin release kinetics was studied with the perifusion sys-tem.Moreover, qRT-PCR and western blot was employed for the mRNA and protein detection of GLUT-2 and GCK.Results In 30, 60, 120 min after the sugar load, the blood sugar level of Xuezhikang group were significantly lower than that of the db/db group (all P<0.05), but they were significantly higher than that of the db /m group (all P<0.05);the level of plas-ma insulin after30 min in Xuezhikang group was significantly higher than that in the db /db group (all P<0.05).Compared with the db/db group, the insulin secretion of Xuezhikang group was not obviously increased for low level glucose perfusion in 2.8 mmol/L, however increased significantly after high level glucose stimulation with 16.7 mmol/L for 1 min (P<0.05), but it was still significantly lower than that in the db/m group (P<0.05).The mRNA and protein expression levels of GLUT-2 and GCK in the db/db group were significantly lower than those in the db/m group (all P<0.05), and the expression lev-els in Xuezhikang group were significantly higher than those in the db/db group( all P<0.05).Conclusion Xuezhikang can improve the secretion of pancreatic islets by increasing the expression of GLUT-2 and GCK in pancreatic islet beta cells .