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胰岛β细胞游离脂肪酸受体1表达对胰岛素分泌的影响 被引量:1

Effect of the expression of free fatty acid receptor 1 on the insulin secretion of β cells
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摘要 目的研究高脂、罗格列酮和非诺贝特对体外培养的β细胞瘤细胞系NIT-1细胞游离脂肪酸受体1(FFAR1)mRNA表达和胰岛素分泌功能的影响。方法将NIT-1细胞随机分为正常组(NC组)、高脂组(PA组)、高脂加罗格列酮组(RG组)、高脂加非诺贝特组(FF组)体外培养48 h,用放免法检测细胞基础胰岛素分泌(BIS)及葡萄糖刺激的胰岛素分泌(GSIS)水平,酶法检测胞内甘油三酯(TG)含量,RT-PCR技术检测细胞内FFAR1 mR-NA水平。结果与NC组比较,PA组GSIS降低,细胞内TG含量增多,FFAR1 mRNA表达明显上调。与PA组比较,RG、FF组GSIS增强,细胞内TG含量减少;RG组FFAR1 mRNA表达与之接近,FF组则明显减少,接近NC组水平。结论高脂对β细胞的毒性作用部分是通过上调FFAR1 mRNA表达所致;非诺贝特可通过抑制这种作用保护β细胞功能;罗格列酮对β细胞功能的保护作用与之无关。 Objective To investigate the effect of palmitic acid, rosiglitazone and fenofibrate on the expression of free fatty acid receptor 1 ( FFAR1 ) and the insulin secretion function of NIT-1 cells were cultured in vitro. Methods NIT-I cells were divided into four groups, nonmal group (NC group), palmitic acid group (PA group), palmitic acid plus rosiglitazone group ( RG group) and palmitic acid plus fenofibrate group ( FF group), then cultured respectively for 48 h in vitro. The levels of insulin secretion were detected with radioimmunoassay, intracellular tfiglycerides contents were determined by enzyme immunoassay and FFAR1 mRNA levels were detected by RT-PCR. Results Compared to the NC group, the GSIS in the PA group decreased, while the level of TG and expression of FFAR1 mRNA increased. Compared o the PA group, GSIS in RG and FF group increased, TG decreased, while the expression of FFAR1 mRNA in FF group decreased too. Conclusions It is one of the mechanisms of lipotoxicity to upregulate the expression of FFAR1 mRNA, and fenofibrate can inhibit it. Rosiglitazone can protect the function of beta cells, but it has nothing to do with the mechanisms above.
出处 《山东医药》 CAS 北大核心 2008年第48期15-17,共3页 Shandong Medical Journal
基金 湖北省自然科学基金资助项目(2003ABA143)
关键词 游离脂肪酸受体1 棕榈酸 罗格列酮 非诺贝特 胰岛素分泌 甘油三酯 free fatty acid receptor 1 palmitie acid rosiglitazone fenofibrate insulin secretion triglyeride
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参考文献9

  • 1Itoh Y, Kawamata Y, Harada M, et al. Free fatty acids regulate insulin secretion from pancreatic beta cells through GPR40[ J]. Nature, 2003,422 (6928) : 173-176.
  • 2Briscoe CP, Tadayyon M, Andrews JL, et al. The orphan G proteincoupled receptor GPR40 is activated by medium and long chain fatty acids[J]. J Biol Chem, 2003,278(13) :11303-11311.
  • 3Steneberg P, Rubins N, Bartoov-Shifman R, et al. The FFA receptor GPR40 links hyperinsulinemia, hepatic steatosis, and impaired glucose homeostasis in mouse[J]. Cell Metab, 2005,1 (4) :245- 258.
  • 4Shapiro H, Shachar S, Sekler 1, et al. Role of GPR40 in fatty acid action on the beta cell line INS-1E[J]. Biochem Biophys Res Commun, 2005,335( 1 ) :977104.
  • 5张丽,高聆,梁军,赵家军.棕榈酸对胰岛的脂毒性及非诺贝特的保护作用[J].中华内分泌代谢杂志,2005,21(2):155-158. 被引量:38
  • 6Lupi R, Del Guerra S, Marselli L, et al. Rosiglitazone prevents the impairment of human islet function induced by fatty acids : evidence for a role of PPARgamma2 in the modulation of insulin secretion [J]. Am J Physiol Endocrinol Metab, 2004,286(4) :560-567.
  • 7Yaney GC, Corkey BE. Fatty acid metabolism and insulin secretion in pancreatic beta cells [ J ]. Diabetologia, 2003,46 ( 10 ) : 1297- 1312.
  • 8Rubi B, Antinozzi PA, Herrero L, et al. Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion [ J]. Biochem J, 2002,364(pt 1 ) :219-226.
  • 9Patane 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.

二级参考文献12

  • 1Shang W, Yasuda K, Takahashi A, et al. Effect of high dietary fat on insulin secretion in genetically diabetic Goto-Kakizaki rats. Pancreas, 2002,25:393-399.
  • 2Holness MJ, Smith ND, Greenwood GK, et al. Acute (24 h) activation of peroxisome proliferator-activated receptor-alpha (PPAR alpha) reverses high-fat feeding-induced insulin hypersecretion in vivo and in perifused pancreatic islets. J Endocrinol, 2003,177:197-205.
  • 3Yoshikawa H, Tajiri Y, Sako Y, et al. Effects of free fatty acids on beta-cell functions: a possible involvement of peroxisome proliferator-activated receptors alpha or pancreatic/duodenal homebox. Metabolism, 2001,50:613-618.
  • 4Lupi R, Dotta F, Marselli L, et al. Prolonged exposure to free fatty acids has cytostatic and pro-apoptotic effects on human pancreatic islets: evidence that beta-cell death is caspase mediated, partially dependent on ceramide pathway, and Bcl-2 regulated. Diabetes, 2002,51:1437-1442.
  • 5Dixon G, Nolan J, McClenaghan NH, et al. Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity. Clin Sci (Lond), 2004,106:191-199.
  • 6Komatsu M, Sato Y, Yamada S, et al. Triggering of insulin release by a combination of cAMP signal and nutrients: an ATP-sensitive K+ channel-independent phenomenon. Diabetes, 2002,51(Supl 1):S29-S32.
  • 7Sugden MC, Holness MJ. Potential role of peroxisome proliferator-activated receptor-alpha in the modulation of glucose-stimulated insulin secretion. Diabetes, 2004,53(Suppl 1):S71-S81.
  • 8Koh EH, Kim MS, Park JY, et al. Peroxisome proliferator-activated receptor (PPAR) -α activation prevents diabetes in OLETF Rats: comparison with PPAR-γ activation. Diabetes, 2003,52:2331-2337.
  • 9Briaud I, Kelpe CL, Johnson LM, et al. Differential effec ts of hyperlipidemia on insulin secretion in islets of langerhans from hyperglycemic versus normoglycemic rats. Diabetes, 2002,51:662-668.
  • 10Wang H, Maechler P, Ritz-Laser B, et al. Pdx level defines pancreatic gene expression pattern and cell lineage differention. J Biol Chem, 2001,276:25279-25286.

共引文献37

同被引文献20

  • 1Corkey BE, Deeney JT, Yaney GC, et al. The role of long-chain fatty acyl- CoA esters in 13 cell signal transduction[ J]. Nutr,2000,130:299-304.
  • 2Itoh Y, Kawmata Y, Harada M, et al. Free fatty acids regulate insulin se- cretion from pancreation beta cells through GPR40 [ .l ]. Nature, 2003, 422 : 173-176.
  • 3McGarry JD. Banting Lecture 2001 :Dysregulation of fatty acid metaolism in the etiology of type 2 diabetes[ J]. Diabetes ,2002,51 ( 1 ) :7-18.
  • 4Stein DT, Stevenson BE, Chester MW, et al. The insulinotropic potency of fatty acides is influenced profoundly by their chain length and degree of saturation[ J]. Clin Invest, 1997,100:398-403.
  • 5Yaney GC, Corkey BE. Fatty acid metabolism and insuin secretion in pancreatic beta ceils[ J]. Diabetologia,2003,46 : 1297-1312.
  • 6Sawzdargo M, George SR, Nguyen T, et al. A cluster of four novel human G protein-coupled receptor genes occuring in close proximity to CD22 gene on chromosome 19q13. 1 [ J ]. Biochem Biophys Res Commun, 1997,239:543-547.
  • 7Kotarsky K, Nilsson NE, Flodgren E, et al. A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs [ J]. Biochem Biophys Res Commun ,2003,301:406-410.
  • 8Briscoe CP, Tadayyon M, Andrews JL, et al. The orphan G protein-cou- pled receptor GPR40 is activated by medium and long chain fatty acids [ J ]. J Biol Chem ,2003,278 : 11303-11311.
  • 9Tomita T, Masuzaki H, Iwakura H, et al. Expression of the gene for a membrane-bound fatty acid receptor in the pancreas and islet cell tumours in humans: evidence for GPR40 expression in pancreatic beta cells and implications for insnlin secretion [ J ]. Diabetologia, 2006,49 (3) :962-968.
  • 10Kebede M, Alquier T, Latour MG, et al. The fatty acid receptor GPR40 plays a role in insulin secretion in vivo after high-fat feeding[ J]. Dia- betes ,2008,57:2432-2437.

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