糖毒性对TC1—6细胞胰升糖素分泌的影响  

Impact of glucotoxicity on TC1-6 cell glucagon secretion

作　　者：沈晓霞[1] 李宏亮[1] 洪靖[1] 校娟[1] 侯志强[1] 潘琳[1] 王长征[2] 李光伟[1] 

机构地区：[1]卫生部中日友好医院内分泌代谢病中心,北京100029 [2]美国芝加哥大学药学实验室

出　　处：《中华内分泌代谢杂志》2009年第1期9-12,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的探讨长期糖毒性对胰岛α细胞胰升糖素分泌的影响及其与α细胞胰岛素抵抗的关系。方法TC1-6细胞（α细胞株）分别培养于含低浓度（5．5mmol／L）、中浓度（11．1mmol／L）和高浓度（25mmol／L）葡萄糖的培养基中1～5天，检测胰升糖素分泌及其mRNA表达；加入不同浓度胰岛素6h后，观察对培养5天的TC1-6细胞胰升糖素分泌的影响并以Western印迹检测高糖对TC1-6细胞Akt磷酸化的影响。结果（1）与低糖培养相比，中、高浓度葡萄糖培养1天和3天的TC1-6细胞胰升糖素分泌无明显改变，而高糖培养5天时TC1-6细胞的胰升糖素分泌明显增高[（136．80±10．94vs78．62±4．72）ng／10^6细胞，P〈0．05]；另外，培养5天时胰升糖素mRNA的表达较1天时明显升高（P〈0．05）；（2）10^-7mol／L胰岛素抑制低糖组TC1-6细胞胰升糖素的分泌[（21．59±1．30vs55．12±3．86）ng／10^6细胞]，但仅能轻微抑制高糖组胰升糖素的分泌[（106．58±8．53vs117．18±10．55）ng／10^6细胞]；当胰岛素增至10^-5mol／L时，高糖组胰升糖素的分泌也受到抑制[（46．55±3．72vs118．61±10．68）ng／10^6细胞]；（3）加入10^-5mol／L胰岛素2h后，两组TC1-6细胞磷酸化Akt水平分别升高180％和70％，但高糖组明显低于低糖组，给予磷脂酰肌醇3激酶抑制剂后两组TC1-6细胞磷酸化Akt水平在低糖组抑制率明显高于高糖组。结论高糖可增加TC1-6细胞胰升糖素的分泌，其可能的机制与TC1-6细胞胰岛素抵抗有关。Objective To investigate the effects of chronic high glucose on α-cells glucagon releasing in relation to insulin resistance induced by high glucose. Methods TC1-6 cells, an α-cell line, were incubated separately in DMEM containing high （ 25. 0 mmol/L ） , medium （ 11. 1 mmol/L ） and low （ 5. 5 mmol/L ） concentrations of glucose for 1 to 5 days. The secretion and gene expression of glucagon were measured. When TC1-6 ceils had been cultured for 5 days, three different concentrations of insulin were added for 6 h and then glucagon secretion was detected. Western blot was used for 1 and 3 days to confirm the effect of high glucose on phosphorylation of Akt in TC1-6 cells. Results （ 1 ） Exposure of TC1-6 cells to 11.1 and 25.0 mmol/L glucose resulted in a slight increase of glucagon secretion compared with those incubated with 5.5 mmol/L. However, after 5 days in media containing 25.0 mmol/L glucose, glucagon secretion was significantly increased as compared to ceils treated with low glucose [ （ 136.80±10.94 vs 78.62±4.72） ng/10^6 ceils, P〈0.05 ] ; moreover, in TC1-6 cell cultured with high glucose glucagon mRNA expression was increased significantly. （2） 10^-7 mol/L insulin reduced significantly glucagon secretion of TC1-6 cells exposed to low glucose [ （ 21.59 ± 1.30 vs 55. 12 ± 3.86 ） ng/10^6 cells], but just scarcely inhibited glucagon secretion of cells incubated with high glucose [ （106.58±8.53 vs 117.18±10.55） ng/10^6 cells]. When insulin concentration was increased to 10^-5 mol/L, glucagon secretion of TC1-6 cells in high glucose was also reduced [ （46.55 ±3.72 vs 118.61 ± 10.68 ）ng/10^6 cells ]. （3） After treated with 10^-5 mol/L insulin for 2h, the levels of Akt phosphorylation in both groups of TC1-6 cells were increased by 180% and 70%, while the level in high glucose group was significantly lower than that in low glucose group. In the presence of phosphoinositide 3 kinase inhibitor, the levels of Akt phosphorylation were both lowered, but the inhibition

关 键 词：高糖 胰岛素抵抗 胰岛素信号通路 

分 类 号：R686[医药卫生—骨科学]