期刊文献+

胰高血糖素样多肽-1拮抗2型糖尿病胰岛细胞凋亡损伤(英文) 被引量:2

GLP-1 Antagonizes the Apoptosis of T2DM Islet Cells
下载PDF
导出
摘要 胰高血糖素样多肽-1(glucogen-like peptide-1,GLP-1)在胰岛素分泌过程中扮演重要角色,并在改善β细胞功能方面有着令人瞩目的效应,但有关其作用机制尚需更深入研究。本研究探讨GLP-1对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠模型胰岛细胞损伤的影响,观察GLP-1在T2DM大鼠胰岛细胞凋亡损伤机制中所发挥的作用。HE染色结果发现,糖尿病大鼠胰岛损伤。ELISA结果表明,糖尿病患者和糖尿病大鼠血清中GLP-1表达水平上调。放射免疫结果表明,GLP-1和谷氧还蛋白1(Grx1)促进HIT-T 15细胞分泌胰岛素,Cd抑制胰岛素的分泌。免疫组化结果表明,糖尿病大鼠GLP-1加药处理后,各组与糖尿病组相比,药物提高了Grx1和胰岛素表达水平,降低了胰高血糖素表达水平,同时降低了活性胱天蛋白酶3(caspase-3)的表达。本研究结果提示,GLP-1在肥胖T2DM大鼠胰岛细胞凋亡中起保护作用,同时可调节胰岛素和胰高血糖素水平,其机制可能与Grx1相关。 Glucagon-like peptide-1 (GLP-1) plays an important role during insulin secretion and has a remarkable effect on improving the function of β cells. However, the mechanisms of GLP-1 needs to be further elucidated. The purpose of this study was to investigate the effects of GLP-1 on pancreatic islet cell damage in type 2 diabetes mellitus (T2DM) rats, and to observe the role of GLP-1 in the apoptosis of islet cells in T2DM rats. The results of HE (hematoxylin-eosin) staining revealed islet damage in T2DM rats. ELISA results showed that the level of GLP-1 was up-regulated in serum of T2DM patients and T2DM rats. The results of radioimmunoassay showed that GLP-1 and glutaredoxin 1 (Grx1) promoted insulin secretion, and Cd inhibited insulin secretion in HIT-T 15 cells. Immunohistochemical results showed that GLP-1 increased the expression levels of Grx1 and insulin, and decreased the expression level of glucagon and active caspase-3 in islet cells of T2DM rats. These results indicated that GLP-1 plays a protective role in the apoptosis of islet cells in obese T2DM rats and regulates the levels of insulin and glucagon, and its mechanism may be related to Grx1.
作者 刘颖 程昊 孙晓杰 齐晓丹 朱文斌 师岩 徐晶 李淑艳 衣同辉 陈影 于海涛 赵正林 张春晶 LIU Ying;CHENG Hao;SUN Xiao-Jie;QI Xiao-Dan;ZHU Wen-Bin;SHI Yan;XU Jing; LI Shu-Yan;YI Tong-Hui;CHEN Ying;YU Hai-Tao;ZHAO Zheng-Lin;ZHANG Chun-Jing(Department of Biochemistry,Qiqihar 161006,Heilongjiang,China;Third Affiliated Hospital,Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China;Department of Clinical Biochemistry,Qiqihar 161006,Heilongjiang,China;Department of Tumor Molecular Biology,Qiqihar 161006,Heilongjiang,China;Department of Biology Genetics,Qiqihar Medical University,Qiqihar 161006,Heilongjiang,China)
出处 《中国生物化学与分子生物学报》 CAS CSCD 北大核心 2018年第12期1342-1349,共8页 Chinese Journal of Biochemistry and Molecular Biology
基金 Supported by Postdoctoral Researcher of Heilongjiang Postdoctoral Management Office(No.LBH-Q16225) Qiqihar Medical University(No.QY2016LX-01 and QY2016B-36)~~
关键词 谷氧还蛋白1 胰高血糖素样多肽 胱天蛋白酶3 胰岛素 胰高血糖素 glutaredoxin 1 glucogen-like peptide-1 caspase-3 insulin glucagon
  • 相关文献

参考文献8

二级参考文献86

  • 1Xin-jia WANG,Kang-mei KONG,Wei-li QI,Wei-lian YE,Pei-song SONG.Interleukin-1 beta induction of neuron apoptosis depends on p38 mitogen-activated protein kinase activity after spinal cord injury^1[J].Acta Pharmacologica Sinica,2005,26(8):934-942. 被引量:19
  • 2高虹,宁光.胰高血糖素样肽1的胰腺外作用研究进展[J].国际内科学杂志,2007,34(7):408-411. 被引量:25
  • 3Doyle ME, Egan JM. Mechanisms of glucagon-like peptidel in the pancreas [ J ]. Pharmacol Ther,2007,113 ( 3 ) :546-593.
  • 4Kim W, Egan JM. The role of inm'etins in glucose homeostasis and diabetes treatment [J]. Pharmacol Rev,2008,60 (4) :470-512.
  • 5Farilla L, Bulotta A, Hirshberg B, et al. Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets[ J]. Endocrinology,2003,144:5149-5158.
  • 6Drucker DJ, Philippe J, Mojsov S, et al. Glucagon-like peptide I stimulates insulin gene expression and increases cyclic AMP levels in a rat islet cell line[ J]. Proc Natl Acad Sei USA, 1987,84(10) :3434- 3438.
  • 7Buteau J, Roduit R, Susini S, et al. Glucagon-like peptide-1 promotes DNA synthesis, activates phosphatidylinositol 3-kinase and increases transcription factor pancreatic and duodenal homeobox gene 1 ( PDX- 1 ) DNA binding activity in beta ( INS-1 ) -cells [ J ]. Diabetologia, 1999,42 ( 7 ) : 856 -864.
  • 8Zhao T, Parikh P, Bhashyam S, et al. Direct effects of glucagon-like peptide-1 on myocardial contractility and glucose uptake in normal and postischemic isolated rat hearts [ J ]. J Pharmacol Exp Ther, 2006,317:1106-1113.
  • 9Nikolaidis LA, Doverspike A, Hentosz T, et al. Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines [ J ]. J Pharmacol Exp Ther, 2005,312( 1 ) :303-308.
  • 10Wettergren A, Schjodager B, Mortensen PE, et al. Truncated GLP-1 (proGlucaGon 78-107 amide) inhibits gastric and pancreatic functions in man[J]. Dig Dis Sci,1993,38:665.

共引文献50

同被引文献15

引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部