期刊文献+

球形脂联素对胰岛β细胞胰岛素分泌和凋亡的影响 被引量:8

Effects of globular adiponectin on insulin secretion and apoptosis of pancreatic β cells
原文传递
导出
摘要 目的观察脂联素对胰岛β细胞胰岛素分泌、UCP-2、PPARγmRNA表达和凋亡的影响。方法大鼠胰岛细胞株RIN-m5F分别用5.6mmol/L和16.7 mmol/L葡萄糖,并加入不同浓度的球形脂联素(0~2500μg/L)培养48 h。放免法测定胰岛素含量,RT-PCR检测UCP-2、PPARγmRNA的表达。流式细胞仪检测细胞凋亡率,Western Blot检测激活型Caspase3的表达。结果高糖培养下脂联素同时干预后基础胰岛素分泌显著降低,高糖刺激的胰岛素分泌显著增加。和高糖组比较,脂联素组UCP-2、PPARγmRNA的表达显著降低(P<0.05),细胞凋亡率和激活型Caspase-3的表达显著降低(P<0.05)。结论脂联素能改善高糖所致的β细胞胰岛素分泌异常,其机制可能与通过下调PPARγ降低UCP-2的表达有关。脂联素可拮抗高糖所致的β细胞凋亡。 Objective To observe the effects of globular adiponectin on insulin secretion function, mRNA expression of UCP 2 and PPARγand apoptosis in pancreatic - cells. Methods Rat insulinoma cell line RIN-mSF was cultured in 5.6 mmol / L glucose and 16.7retool / L glucose respectively, with or without different concentration of rat globular adiponectin intervention(0 - 2500μg/l)for 48 hours. Basal and high glucose- stimulated insulin secretion (GSIS)in the medium was measured by radioimmunoassay (RIA). UCP-2 and PPARγ mRNA expression in β cells was detected by RT PCR. Ceil apoptosis was detected by flow cytometric analysis and the protein expression leveI of cleaved easpase 3 was detected by Western blot. Results Basal insulin secretion significantly decreased but GSIS significantly increased after adiponectin intervention under high glucose condition. Compared with control group, UCP-2 and PPAR7 mRNA expression significantly increased in high glucose group (P〈 0.05), but it decreased in group with adiponectin intervention(P〈0.05). After co-incubation with adiponectin, apoptotic cells and the protein expression level of cleaved caspase 3 were significantly decreased compared with that of the high glucose group(P〈0.05). Conclusions Adiponectin can restore the secretion fuction of 13 cells impaired by chronic exposure to high glucose level, which may be related to the mechanism of reduced UCP-2 mRNA expression regulated by adiponectin through PPAR7 pathway. Adiponectin can counteract high glucose -induced apoptosis of the pancreatic beta cells by inhibiting caspase-3 activation.
出处 《中国糖尿病杂志》 CAS CSCD 北大核心 2010年第12期930-933,共4页 Chinese Journal of Diabetes
基金 国家自然科学基金资助项目(30570756)
关键词 脂联素 胰岛细胞 解偶联蛋白2 过氧化物酶体激增剂激活受体 凋亡 Adiponectin Islet cells Uncoupling protein-2, Peroxisome proliferator activatedpeceptor Apoptosis
  • 相关文献

参考文献9

  • 1Noriyuki Ouchi,Kenneth Walsh.Adiponectin as an anti-inflammatory factor.Clinica Chimica Acta,2007,380:24-30.
  • 2Staiger K,Stefan N,Staiger H,et al.Adiponectin is functionally active in human islets but does not affect insulin secretory function or β-cell lipoapoptosis.J Clin Endocrinol Metab,2005,90:6707-6713.
  • 3Gu W,Li X,Liu C,et al.Globular adiponectin augments insulin secretion from pancreatic islet beta cells at high glucose concentrations.Endocrinology,2006,30:217-221.
  • 4Okamoto M,Ohara-lmaizumi M,Kubota N,et al.Adiponectin induces insulin secretion in vitro and in vivo at a low glucose concentration.Diabetologia,2008,51:827-835.
  • 5任冬月,赵晓娟.解偶联蛋白2在高糖致大鼠胰岛β细胞功能障碍中的作用[J].中国医科大学学报,2007,36(3):293-294. 被引量:4
  • 6Ito E,Ozawa S,Takahashi K,et al.PPAR-γoverexpression selectively suppresses irsulin secretory capacity in isolated pancreatic islets through induction of UCP-2 protein.Biochem Biophys Res Commun,2004,324:810-814.
  • 7Patane G,Anello M,Piro S,et al.Role of ATP production and uncoupling protein 2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator activated receptor gamma inhibition.Diabetes,2002,51:2749-2756.
  • 8Lin P,Chen Li,Li D,et al.Adiponectin reduces glucotoxicityinduced apoptosis of INS-1 rat insulin-secreting cells on a microfluidic chip.Tohoku J Exp Med,2009,217:59-65.
  • 9Rakatzi I,Mueller H,Ritzeler O,et al..Adiponectin counteracts cytokine-and fatty acid-induced apoptosis in the pancreatic beta-cell line INS-1.Diabetologia,2004,47:249-258.

二级参考文献10

  • 1ZHANG CY, BAFFY G, PERRET P, et al. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes [J]. Cell, 2001, 105(6) :745 -755.
  • 2PATANE G,ANELLO M,PIRO S,et al. Role of ATP production and uncoupling protein-2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator-activated receptor-gamma inhibition [J]. Diabetes, 2002,51 ( 9 ) :2749 - 2756.
  • 3LAYBUTT D R,SHARMA A,AGROI DC, et al. Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia [J]. J Biol Chem,2002,277 ( 13 ) : 10912 - 10921.
  • 4LIU M ,SHAPIRO M E. A new method for isolation of murine islets with markedly improved yields [ J ]. Transplantation Proceedings, 1995,27(6) :3208 -3210.
  • 5ZHOU Y T,SHIMABUKURO M, KOYAMA K, et al. Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation [J]. Proc Natl Acad Sci USA,1997,94(12) : 6386 -6390.
  • 6ASHCROFF FM, GRIBBLE FM. ATP-sensitive K^+ channels and insulin secretion : their role in health and disease [ J ]. Diabetologia, 1999,42 (8) :903 - 919.
  • 7CHAN CB, DE LEO D, JOSEPH JW, et al. Increased UCP2 level β cells are associated with impaired glucose-stiulated insulin secretion:mechanism of action [J]. Diabetes, 2001,50 ( 6 ) : 1302 - 1310.
  • 8PATANE G, ANELLO M, PIRO S, et al. Role of ATP production and uncoupling protein-2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator-activated receptor-gamma inhibition [ J ]. Diabetes,2002,51 (9) :2749 - 2756.
  • 9CATHERINE EG, MICHAEL G, JAMIE SH, et al. Determinants of glucose toxicity and its reversibility in the pancreatic islet b-cell line, HIT-T15 [J]. Am J Physiol Endocrinol Metab, 2000,279 (5) :E997 - E1002.
  • 10STEFAN K, CHEN-YU ZHANG, LUCA S, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic β cell dysfunction[J]. J Clin Invest ,2003,112 ( 12 ) : 1831 - 1842.

共引文献3

同被引文献63

引证文献8

二级引证文献34

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