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3T3-L1脂肪细胞中葡萄糖转运蛋白和己糖摄取的调节:胰高血糖素样肽-1与胰岛素的相互作用

Regulation of glucose transporters and hexose uptake in 3T3-L1 adipocytes: glucagon-like peptide-1 and insulin interactions.

作者信息

Wang Y, Kole H K, Montrose-Rafizadeh C, Perfetti R, Bernier M, Egan J M

机构信息

National Institute on Aging/Gerontology Research Center, Diabetes Section, Baltimore, Maryland 21224, USA.

出版信息

J Mol Endocrinol. 1997 Dec;19(3):241-8. doi: 10.1677/jme.0.0190241.

DOI:10.1677/jme.0.0190241
PMID:9460645
Abstract

Glucagon-like peptide-1 (7-36 amide) (GLP-1) is known to increase insulin release when given as a bolus in the fasted and fed state. GLP-1 also increases glucose uptake and lipid synthesis in cultured adipocytes. In this study we investigated the effects of GLP-1 on glucose uptake and on the levels of expression of the facilitative glucose transporters, GLUT1 and GLUT4, in fully differentiated 3T3-L1 adipocytes. Cells were incubated with GLP-1 (10 nM) with or without insulin (10 and 100 nM) for 24 h. Under these conditions, GLP-1 alone caused an increase in basal and acute insulin-stimulated glucose uptake along with an increase in GLUT1 and GLUT4 protein levels. However, there was no change in the expression of GLUT1 and GLUT4 mRNAs. In the absence of GLP-1, prolonged exposure to insulin caused a marked reduction in the levels of GLUT4 mRNA and protein, and an inhibition of glucose uptake after an acute exposure to insulin. This insulin-induced down-regulation of GLUT4 was prevented when GLP-1 was present during the 24-h treatment. In contrast, the acute insulin-stimulated glucose uptake could not be restored by GLP-1. GLP-1 is therefore the first gut hormone shown to be capable of modulating glucose transporter levels in cultured adipocytes.

摘要

胰高血糖素样肽-1(7-36酰胺)(GLP-1)已知在空腹和进食状态下推注给药时可增加胰岛素释放。GLP-1还可增加培养的脂肪细胞中的葡萄糖摄取和脂质合成。在本研究中,我们研究了GLP-1对完全分化的3T3-L1脂肪细胞中葡萄糖摄取以及易化性葡萄糖转运蛋白GLUT1和GLUT4表达水平的影响。将细胞与GLP-1(10 nM)一起孵育,有无胰岛素(10和100 nM),孵育24小时。在这些条件下,单独的GLP-1导致基础和急性胰岛素刺激的葡萄糖摄取增加,同时GLUT1和GLUT4蛋白水平增加。然而,GLUT1和GLUT4 mRNA的表达没有变化。在没有GLP-1的情况下,长时间暴露于胰岛素会导致GLUT4 mRNA和蛋白水平显著降低,并且在急性暴露于胰岛素后会抑制葡萄糖摄取。当在24小时治疗期间存在GLP-1时,这种胰岛素诱导的GLUT4下调被阻止。相比之下,GLP-1不能恢复急性胰岛素刺激的葡萄糖摄取。因此,GLP-1是第一种被证明能够调节培养的脂肪细胞中葡萄糖转运蛋白水平的肠道激素。

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