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目的 探讨辣椒素对小鼠瘤β TC-6细胞胰岛分泌功能的作用及其相关的降糖机制.方法 (1)辣椒素对小鼠瘤β TC-6细胞增殖率的影响:在不同浓度的辣椒素(0、10、50、100、200、300 μmol/L)作用下,测定小鼠瘤β TC-6细胞的增殖率、胰岛素分泌量和胞内Ca2+的浓度;(2)辣椒素受体(TRPV1)调控试验:筛选合适剂量辣椒素(50 μmol/L)和辣椒卓平(15 μmol/L),培养48 h后测定TRPV1、胰腺十二指肠同源异形盒1(PDX-1)、胰岛素受体底物1 (IRS1)、胰岛素受体底物2(IRS2)和葡萄糖转运蛋白2(GLUT2)在β TC-6细胞中的蛋白水平.结果 辣椒素能够抑制β TC-6细胞增殖,其胞内Ca2+浓度与胰岛素分泌功能密切相关,且辣椒素能显著上调TRPV1、PDX-1、IRS1、IRS2和GLUT2的蛋白水平,但TRPV1通道被辣椒卓平阻断后,这种上调作用显著减弱.结论 (1)在辣椒素剂量为0~50 μ mol/L条件下,β TC-6胞内Ca2+浓度与其胰岛素分泌量正相关;(2)辣椒素对胰岛细胞的刺激是其降糖作用的主要来源,与胰岛细胞的增殖无关,且胰岛细胞中可能存在TRPV1-PDX-1-GLUT2/IRS1信号通路.“,”Objective To study the effect of capsaicin on stimulating the βTC-6 mouse insulinoma cells and related mechanism.Methods (1) The influence of capsaicin on βTC-6 cell proliferation rate,insulin secretion and intracellular Ca2+ concentration of βTC-6 cell were measured under the different concentrations of capsaicin (0,10,50,100,200 and 300 μmol/L);(2) The protein levels of transient receptor potential vanilloid 1 (TRPV1),pancreatic duodenum homeobox 1 (PDX-1),insulin receptor substrate 1 (IRSI),insulin receptor substrate 2 (IRS2) and glucose transport protein 2 (GLUT2) in βTC-6 cells were measured after cultured 48 hours with the addition of capsaicin (50 μmol/L) and capsazepin (15 μmol/L).The dosage used in the experiment was based on βTC-6 cell proliferation experiment.Results Cell proliferation was markedly inhibited by capsaicin.The intracellular Ca2+ concentration in βTC-6 cells was closely related to insulinm secretion.More importantly,the protein levels of TRPV1,PDX-1,IRS1,IRS2 and GLUT2 were significantly up-regulated by capsaicin.However,this up-regulation was significantly reduced after the TRPV1 ion channels was blocked by capsazepin.Conclusion (1) The positive correlations between intracellular Ca2+ concentration and insulin secretion were observed when the concentration of capsaicin ranged from 0 to 50 μtmol/L;(2) The hypoglycemic effect of capsaicin was mainly contributed by its stimulation effect on islet cells,not by proliferation of islet cells.The signaling pathways of TRPV1-PDX-1-GLUT2/IRS1 may co-exist in islet cells.