文献类型：期刊文献

中文题名：FGF-21与胰岛素在调节糖代谢过程中的协同作用及其机制

英文题名：The synergistic effect of FGF-21 and insulin on regulating glucose metabolism and its mechanism

作者：于丹[1];孙翠羽[1];孙国鹏[2];任桂萍[1];叶贤龙[1];朱升龙[1];王文飞[1];徐鹏飞[1];厉书杰[1];吴强[1];牛泽杉[1];孙田[1];刘铭瑶[1];李德山[1]

第一作者：于丹

机构：[1]东北农业大学生命科学学院;[2]新乡学院生命科学与技术系

第一机构：东北农业大学生命科学学院,黑龙江哈尔滨150030

年份：2014

卷号：49

期号：7

起止页码：977-984

中文期刊名：药学学报

外文期刊名：Acta Pharmaceutica Sinica

收录：CSTPCD;;Scopus;北大核心:【北大核心2011】；CSCD:【CSCD2013_2014】；PubMed;

基金：黑龙江省发展和改革委员会重大前期项目(黑发改项目[2011]1570号);黑龙江省博士后科研启动基金项目(LBH-Q09162);黑龙江省教育厅科学技术研究项目(12521z004);国家自然基金东北农业大学生物学理科基地科研训练及科研能力提高项目(J1210069/J0106)

语种：中文

中文关键词：糖尿病;FGF-21;胰岛素;协同作用

外文关键词：diabetes mellitus; fibroblast growth factor-21; insulin; synergy

摘要：本研究旨在阐明FGF-21与胰岛素在调节糖代谢过程中的协同作用机制。通过检测FGF-21或(和)胰岛素作用后,HepG2胰岛素抵抗细胞模型葡萄糖的吸收率以及2型糖尿病db/db小鼠血糖变化,证明FGF-21和胰岛素具有协同作用;采用real-time PCR方法检测肝脏中GLUT1和GLUT4转录水平,揭示两者在调节糖代谢过程中协同作用的机制。实验结果表明,两者在调节糖代谢过程中具有协同作用。Real-time PCR结果表明,FGF-21单独作用可上调GLUT1转录水平,且呈剂量依赖性,而对GLUT4转录水平没有作用;胰岛素(4 u)单独作用组仅上调GLUT4转录水平,而对GLUT1转录水平无影响;FGF-21 0.1 mg·kg-1(无效剂量组)单独作用,GLUT1和GLUT4转录水平均没有改变。但是,当FGF-21 0.1 mg·kg-1(无效剂量)与胰岛素(4 u)共同作用时,GLUT1和GLUT4的转录水平均显著增加,且GLUT1转录水平与5倍浓度的FGF-21单独作用相似,GLUT4转录水平显著高于胰岛素单独作用的效果,说明在FGF-21存在的情况下,胰岛素具有增加FGF-21敏感性的作用;在胰岛素存在的情况下,FGF-21同样具有增加胰岛素敏感性的作用。综上所述,FGF-21与胰岛素在糖代谢过程中的协同作用机制是通过彼此增敏来实现的。
Previous studies proposed that the synergistic effect of fibroblast growth factor-21（FGF-21） and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin（4 u） alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg·kg-1 FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg·kg-1 FGF-21 was used in combination with insulin（4 u） significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin（4 u） alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic effect on glucose metabolism through mutual sensitization.