期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

Exendin-4体外通过抑制NF-κB-iNOS-NO信号减轻氧化应激诱导的小鼠MIN6胰岛β细胞凋亡 被引量：5

Exendin-4 protected murine MIN6 pancreatic β-cells from oxidative stress-induced apoptosis via down-regulation of NF-κB-iNOS-NO pathway
暂未订购
导出
摘要 探讨胰高血糖素样肽-1受体激动剂Exendin-4(Ex-4)在氧化损伤诱导胰岛β细胞凋亡中的保护作用。培养的MIN6胰岛β细胞,通过AO-EB染色观察细胞凋亡形态,Annexin-V-PI染色流式技术测定凋亡率,Griess法检测细胞内一氧化氮水平,Western blotting检测胞浆iNOS蛋白、胞浆及胞核核因子-κBp65(NF-κBp65)蛋白表达水平。Ex-4可抑制叔丁基过氧化氢(t-BHP)诱导的β细胞凋亡,Ex-4(100 nmol.L-1)预处理较单独t-BHP处理,其凋亡率减少约67%(P<0.001)。Ex-4同时减少NO水平的增高,并抑制t-BHP诱导的β细胞NF-κBp65活化及iNOS蛋白表达水平。Ex-4可能通过抑制细胞内NF-κB活化、胞浆iNOS表达来抑制NO水平,最终减轻氧化损伤诱导的β细胞凋亡。 To explore the effect of glucagon-like peptide-1 receptor agonist -Exendin4 （Ex--4）on murine MIN6 pancreatic β-cells apoptosis induced by oxidative stress, the morphological changes of cell damage were evaluated by epifluorescence microscopy after staining with AO-EB. The percentage of cell apoptosis was determined by flow cytometric assay after Annexin-V-FITC-PI staining. Nitric oxide level was measured by Griess reagent assay. Inducible nitric oxide synthase （iNOS） protein and NF-κBp65 fragment were detected by Western blotting. Ex4 inhibited the increase of nitrite level and percentage of apoptosis induced by t-BHP in MIN6 cells. Furthermore, Ex-4 partly reduced the expression of iNOS protein and the ratio of NF-κBp65 protein in nucleus：cytosol induced by t-BHP. These results suggest that Ex-4 protects MIN6 pancreatic β-cells from oxidative stress-induced apoptosis via down-regulation of NF-κB-iNOS-nitric oxide pathway.
作者 刘礼斌 王燕萍 潘晓东 姜苏原 陈洲
机构地区 福建医科大学附属协和医院、福建省内分泌研究所 上海交通大学附属瑞金医院上海市内分泌研究所上海市内分泌肿瘤重点实验室 福建医科大学药学院
出处 《药学学报》 CAS CSCD 北大核心 2008年第7期690-694,共5页 Acta Pharmaceutica Sinica
基金 福建省高等学校新世纪优秀人才支持计划资助(NCETFJ-0703).
关键词 EXENDIN-4 胰岛Β细胞 细胞凋亡 核因子κB 诱导型一氧化氮合酶 一氧化氮 叔丁基过氧化氢 Exendin-4 pancreatic β-cell apoptosis nuclear factor-κB inducible nitric oxide synthase nitric oxide ten-butyl hydroperoxide
分类号 R742.5 [医药卫生—神经病学与精神病学]
  • 相关文献

参考文献10

  • 1List JF, Habener JF. Glucagon-like peptide-1 agonists and the development and growth of pancreatic B-cells [J]. Am J Physiol Endocrinol Metab, 2004,286 :E875 - E881.
  • 2Hui H, Nourparvar A, Zhao X, et al. Glucagon-like- peptide-1 inhibits apoptosis of insulin-secreting cells via a cyclic 5'-adenosine monophosphate-dependent protein kinase A- and a phosphastidylinositol 3-kinase-dependent pathway [ J ]. Eudocrinology, 2003,144 : 1444 - 1455.
  • 3Kaneto H, Fujii J, Seo HG, et al. Apoptotic cell death triggered by nitric oxide in pancreatic beta-cells [ J ]. Diabetes, 1995,44:733 - 738.
  • 4Schreiber E, Matthias P, Mulh.r MM, et al. Rapid detection of oetamer binding proteill- with “miniextracts”, prepared from a small number of cells [ J ]. Nucl Acid Res, 1989,17:6419.
  • 5Baldwin AS Jr. Series introduction: the transcription factor NF-kappaB and human disease [ J ]. J Clin Invest, 2001,107:3 - 6.
  • 6McCabe C, Samali A, O' brien T. Beta cell cytoprotective strategies: establishing the relative roles for iNOS and ROS [ J]. Biochem Biophys Res Commun, 2006,342: 1240 - 1248.
  • 7李强,许霖水.外源一氧化氮对大鼠胰岛细胞损伤机制研究[J].西北国防医学杂志,2002,23(5):361-363. 被引量：14
  • 8Li L, El-Kholy W, Rhodes C J, et al. Glucagon-like peptide-1 protects beta cells from cytokine-indueed apoptosis and necrosis: role of protein kinase B [ J ]. Diabetologia, 2005,48 : 1339 - 1349.
  • 9Stoffers DA, Kieffer T J, Hussain MA, et al. Insulinotropic glucagons-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas [ J ]. Diabetes, 2000,49: 741 - 748.
  • 10Wang Q, Brubaker PL. Glucagon like peptide 1 treatment delays the onset of diabetes in 8 week old db/db mice [ J]. Diabetologia, 2002,45 : 1263 - 1273.

二级参考文献8

  • 1[1]Darville MI,Eizirik DL.Cytokine induction of Fas gene expression in insulin-producing cell requires the transcription factors NF-KB and C/EBP[J].Diabetes,2001,50:1741-1748.
  • 2[2]Bazzan M, Gruden G, Stella S,et al. Microalbuminuria in IDDM is associated with increased expression of monocyte procoagulant activity[J].Diabetologia, 1998, 41(7): 767-779.
  • 3[3]Salvi GE, Beck JD, Offenbacher S.PGE,IL- 1 β,and TNF-α responses in diabetics as modifiers of periodontal disease exprssion [J].AAn Periodontol, 1998,3(1): 40-56.
  • 4[4]Gotch M, Maki T, Satom S,et al.Reproducible high yield of rat islets by stationary in vitro digestion following pancreatic vuctal or portal venous collagenase injection [J]. Transplantation, 1987,43(5): 725-728.
  • 5[5]Mangan DF,Welch GR,Wah SM. Lipopolysaccharide, tumor necrosis factor-α,and IL- 1β prevent programmed cell death (apoposis) in human peripheral blood monocytes [J]. J Immunol, 1991, 146(5): 1541-1545.
  • 6[6]Ross GM, Mcmillan TJ, Wilcox P,et al.The singel cell microgel electrophresis assay(comet assay): Technical aspects and applications [J]. Mut Res, 1995, 337(1): 57-64.
  • 7[7]Heimberg H , Heremans Y, Jobin C,et al.Inhibition of cytokine-induced NF-KB activation by adenovirus-mediated expression of a NF-KB super-repressor prevents β-cell apoptosis [J].Diabetes,2001,50:2219-2224.
  • 8[8]Zumsteg U,Friferio S,Hollander GA.Nitric oxide production and Fas surface expression mediate two independent pathways of ytokine-induced murine β-cell damage[J].Diabetes , 2000,49:39-47.

共引文献13

同被引文献63

  • 1Dupre J, Ross SA, Watson D,et al. Stimulation of insulin secretion by gastric inhibitory polypeptide in man [ J ]. J Clin Endocrinol Metab, 1973,37 ( 5 ) : 826 -828.
  • 2Edholm T, Cejvan K, Abdel-Halim SM, et al. The incretin hormones GIP and GLP-1 in diabetic rats: effects on insulin secretion and small bowel motility [ J ]. Neurogastroenterol Motil, 2009,21 (3) :313-321.
  • 3Vilsbφll T, Brock B, Perrild H,et al. Liraglutide, a once-daily human GLP-I analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus [ ] ]. Diabet Med ,2008,25 (2) : 152- 156.
  • 4Behme MT, Dupre J, McDonald TJ. Glucagon-like peptide 1 improved glycemic control in Type 1 diabetes [ J]. BMC Endocr Disnrd,2003,3( 1 ) :3.
  • 5Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin4) on glycemic control over 30 weeks in patients with Type 2 diabetes treated with metformin and a sulfonylurea[ J]. Diabetes Care ,2005,28 (5) : 1083-1091.
  • 6Gromada J, Ding WG, Barg S, et al. Muhisite regulation of insulin secretion by cAMP-increasing agonists: evidence that glucagon-like peptide 1 and glueagon act via distinel receptors [J]. Pflugers Arch, 1997,434 (5) :515-524.
  • 7Lin YF, Jan YN, Jan LY. Regulation of ATP-sensitive potassium channel function by protein kinase A-mediated phosphorylation in transfected HEK293 cells [ J]. EMBO J,2000,19 (5) :942-955.
  • 8MacDonald PE, EI-Kholy W, Riedel MJ,et al. The muhiple actions of GLP-1 on the process of glucose-stimulated insulin secretion [ J ]. Diabetes,2002,51 ( 3 ) : S434-S442.
  • 9Holz GG. New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-I in pancreatic beta-cells[J].Horm Metab Res,2004,36(11-12) :787-794.
  • 10Shigeto M, Katsura M, Matsuda M, et al.Low, but physiological, concentration of GLP-1 stimulates insulin secretion independent of the cAMP-dependent protein kinase pathway[J].J Pharmacol Sci, 2008,108 ( 3 ) : 274 -279.

引证文献5

二级引证文献14

药学学报
2008年 第7期

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