游离脂肪酸受体的组织分布及GPR40配基对胰岛β细胞胰岛素分泌功能的影响  

Tissue distribution of free fatty acid receptors and effect of GPR40′s ligands on the insulin secretion in pancreatic β cells

作　　者：白月霞[1,2] 韩春光[2] 胡明[3] 宋良文[2] 刘永学[2] 

机构地区：[1]安徽医科大学 [2]军事医学科学院放射与辐射医学研究所,北京100850 [3]中国人民解放军海军总医院病理科,北京100048

出　　处：《安徽医科大学学报》2012年第11期1295-1299,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30973575)

摘　　要：目的检测游离脂肪酸受体(FFARs)在大鼠不同组织中的表达,并探讨GPR40配基对原代培养大鼠胰岛β细胞和INS-1细胞株胰岛素分泌功能的影响。方法通过RT-PCR法检测GPR40、GPR41、GPR43、GPR84、GPR119及GPR120在大鼠不同组织和胰岛β细胞中的表达;以不同浓度的GPR40激动剂GW9508或亚油酸(LA)作用于原代胰岛β细胞2 h后,收集培养上清,用大鼠胰岛素ELISA试剂盒检测胰岛素水平;并检测它们对大鼠胰岛β细胞株INS-1胰岛分泌功能的影响。结果 GPR40在脑、心、脾、结肠组织中表达较高,GPR41除肝外在所测组织中均显著表达,GPR43在脾脏中表达,GPR84和GPR119在脑中表达较高,GPR120在结肠中表达最高;在大鼠原代胰岛细胞中GPR40表达最高;高糖(25 mmol/L)培养条件下,GW9508或LA能促进原代培养胰岛β细胞和INS-1细胞胰岛素的分泌,加入1μmol/L的GW1100后胰岛素分泌量下降(P<0.05,P<0.01,n=3)。结论 FFARs的组织分布具有一定的规律,GPR40是调节胰岛素分泌的重要信号分子,其激动剂GW9508有可能成为治疗糖尿病的新型药物。Objective To determine the free fatty acid receptors＇ expression in different rat tissues and primary cultured islet cells. Further to focus on the hypothesis that GPR40 plays an important role in insulin secretion after being combined with its agonist GW9508 or linoleie acid. Methods Expression of free fatty acid receptors mRNA in various organs of rats and the islet cells were detected by RT-PCR. The insulin levels were detemined by ELISA. Results GPR40 was predominantly expressed in brain, heart, spleen and colon tissue. GPR41 was highly ex- pressed in every tissue except liver, GPR43 was expressed only in spleen, GPRll9 was expressed abundantly in brain and kidney, GPR120 was expressed highest in the colon; The estimated mRNA copy number of the GPR40 gene in isolated islets was higher than that of other genes encoding receptors for FFA ; GW9508 and LA dose stimu- lated insulin secretion in primary islet cells and INS-1 ; GW1100 inhibited GPR40 elevations stimulated by its ago- nist （P 〈 0. 05,P 〈 0. 01, n = 3 ）. Conclusion Our results indicate that GPR40 plays an important role in regula- ting insulin secretion in pancreatic 13 cells. We believe that its agonist GW9508 is expected to become a new drug for the treatment of diabetes.

关 键 词：游离脂肪酸受体 GPR40 胰岛细胞 胰岛素 

分 类 号：R587.1[医药卫生—内分泌] R363[医药卫生—内科学]