摘要
目的观察二肽基肽酶-Ⅳ(DPP-4)抑制剂沙格列汀对自发性2型糖尿病(T2DM)大鼠血清肠促胰素胰高血糖素样肽-1(GLP-1)、葡萄糖依赖性促胰岛素释放肽(GIP)的影响,并探讨其调控机制。方法选取40只OLETF大鼠,随机分为4组:自发性T2DM组,低、中、高剂量组,另选取同种系10只LETO大鼠为对照组。3剂量组给予浓度分别为(0.5 mg/ml、1.0 mg/ml、2 mg/ml)沙格列汀灌胃,自发性T2DM组和对照组给予生理盐水灌胃,1次/d,持续12周。对比灌胃6、12周后各组血清胰高血糖素样肽-1(GLP-1)、葡萄糖依赖性促胰岛素释放肽(GIP)水平;灌胃12周后进行糖耐量试验,并对比各组空腹胰岛素(FINS)水平;灌胃12周后处死取胰脏组织检测并对比胰腺细胞凋亡率、蛋白激酶B(Akt)、叉头转录因子1(FoxO1)、胰十二指肠同源盒因子(Pdx1)、葡萄糖转运子1(GLUT2)、葡萄糖激酶(GCK)mRNA、磷酸化Akt(p-Akt)、磷酸化FoxO1(p-FoxO1)蛋白相对表达量。结果血清GLP-1、GIP、FINS水平、p-Akt/Akt、p-FoxO1/FoxO1值、Pdx1、GLUT2、GCK mRNA和蛋白组间比较,对照组最高、中剂量组其次、低、高剂量组稍低、自发性T2DM组最低,除低、中剂量组比较差异无显著性外(P>0.05),其他每2组间比较差异均有显著性(P<0.05);灌胃第12周血清GLP-1、GIP水平与灌胃第6周比较,3剂量组显著升高(P<0.05),自发性T2DM组显著降低(P<0.05),对照组差异无显著性(P>0.05);自发性T2DM组大鼠在注射葡萄糖后60 min血糖水平达到峰值;对照组及3剂量组在注射后30 min血糖水平达到峰值,且在30~120 min内随时间延长显著降低(P<0.05);糖耐量试验血糖水平、胰腺细胞凋亡率组间比较,对照组最低、中剂量组其次、低、高剂量组稍高,自发性T2DM组最高,除低、中剂量组比较差异无显著性外(P>0.05),其他每2组间比较差异均有显著性(P<0.05)。结论 DPP-4抑制剂可显著促进自发性T2DM大鼠GLP-1、GIP的分泌,调节糖代谢,减少胰岛细
Objective To observe the effect of dipeptidyl peptidase-IV （DPP-4） inhibitor saxagliptin on serum GLP-1 and GIP levels in spontaneously type 2 diabetic rats and to explore their regulatory mechanisms. Methods 40 OLETF rats were randomly divided into four groups： model group, low, middle and high dose groups, and another 10 LETO rats of the same breed were used as control groups. The 3 dose groups were given 0.5 mg/ml, 1.0 mg/ml, 2 mg/ml saxagliptin by gavage, and the model and control groups were given normal saline by gavage once every day for 12 weeks. The levels of glucagon-like peptide-1 （GLP-1） and glucose-dependent insulinotropic peptide （GIP） in each group after 6 and 12 weeks intragastric administration were compared. Glucose tolerance test was performed and the levels of fasting insulin （FINS） after 12 weeks of intragastric administration were compared. After 12 weeks intragastric administration, the pancreatic tissues were sacrificed and the apoptosis rates of pancreatic cells, protein kinase B （Akt）, forkheadtranscription factors1 （FoxO1）, pancreatic duodenal homeobox （Pdx1）, Glucose transporter 1 （GLUT2）, glucokinase （GCK） mRNA, phosphorylated Akt （p-Akt）, phosphorylated FoxO1 （p-FoxO1） protein relative expressions were measured and compared. Results The levels of GLP-1, GIP, FINS and the relative expressions of Pdx1, GLUT2 and GCK mRNA and protein, the values of p-FoxO1/FoxO1, p-FoxO1/FoxO1 were compared between each 2 groups, and the results showed that the indexes of the control group were the highest, the middle dose group the second, the low and high dose groups slightly lower, the model group lowest. There were significant differences between each 2 groups （ P 〈0.05）, without differences between the low and high dose groups （ P 〉0.05）. The levels of serum GLP-1 and GIP after 12 weeks intragastric administration were significantly higher than those after 12 weeks intragastric administration （ P 〈0.05）. The levels of serum GLP-1 an
作者
郭亚菊
张勇军
宋书贤
张琼
GUO Ya-ju ;ZHANG Yong-jun ;SONG Shu-xian(Department of Endocrinology, The Second Affiliated Hospital of Xi＇an Medical College, Xi＇an Shaanxi 710038, China;Department of Internal Medicine, Chenggu County Chinese Medicine Hospital, Chenggu Shaanxi 723200, China)
出处
《临床和实验医学杂志》
2018年第21期2260-2265,共6页
Journal of Clinical and Experimental Medicine
基金
陕西省课题基金资助(编号:s2017-ZDYF-YBXM-SF-2038)
