STUDIES ON THE REGULATION OF THE INSULIN-SENSITIVE GLUCOSE TRANSPORTER--GLUT4

胰岛素敏感性葡萄糖转运蛋白GLUT4的调控研究

• 批准号: 5200377
• 负责人: J EGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200377
• 关键词: 3T3 cells; adipocytes; aging; cell differentiation; gene expression; glucose; glucose metabolism; glucose transporter; growth media; hormone regulation /control mechanism; insulin; messenger RNA; muscle cells; receptor expression; transcription factor

Insulin is necessary for glucose uptake in the periphery. It induces the translocation of GLUT4, a specific insulin-sensitive glucose transporter, to the plasma membrane of fat cells and muscle cells. Chronic elevation of insulin has been known to cause downregulation of this transporter, leading to reduced insulin-mediated glucose uptake. The fact that glucagon-like peptide-1 (GLP-1) an incretin hormone, modulated insulin signalling in the 3T3-L1 adipocytes (Endocrinology 135:2070-2075, 1994) prompted us to investigate the effects of GLP-1 on the GLUT4 transporter in these cells. It appeared that GLP-1 could reverse the downregulation induced by high concentration of insulin on GLUT4 mRNA levels. GLP-1 also caused an increase in the levels of GLUT1 mRNA and protein, GLUt1 being widely distributed among all tissues. In conjunction with these findings, we also showed that the downregulation of GLUT4 mRNA induced by insulin in cells incubated with 22mM glucose could be prevented by reducing the glucose concentration in the medium. The C/EBP family of transcription factors is coexpressed with adipocyte genes (e.g. GLUT4) during the differentiation of 3T3-L1 adipocytes. We looked at the relationship between gadd 153 (which encodes a C/EBP-related protein that lacks a functional DNA-binding domain), C/EBP alpha and GLUT4, and found an association between the mRNA levels for C/EBP and GLUT4 in a variety of culture conditions. It appeared, however, that the levels of gadd 153 mRNA differed from that of C/EBP alpha depending on the glucose levels in the culture medium.

胰岛素是外周葡萄糖摄取所必需的。 它诱导了 GLUT 4，一种特异性胰岛素敏感性葡萄糖转运蛋白， 脂肪细胞和肌肉细胞的质膜。 慢性升高 已知胰岛素会导致这种转运蛋白的下调， 导致胰岛素介导的葡萄糖摄取减少。 的事实 胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素， 3 T3-L1脂肪细胞中的信号传导（Endocrinology 135：2070-2075，1994） 促使我们研究GLP-1对GLUT 4转运蛋白的影响， 在这些细胞中。 GLP-1似乎可以逆转下调 高浓度胰岛素对GLUT 4 mRNA水平的影响。 GLP-1 也引起GLUT 1 mRNA和蛋白水平的增加，GLUt 1 广泛分布于所有组织中。 结合这些 我们的研究结果还表明，GLUT 4 mRNA的下调诱导 在与22 mM葡萄糖孵育的细胞中， 降低培养基中的葡萄糖浓度。 C/EBP家族 转录因子与脂肪细胞基因共表达（例如GLUT 4） 在3 T3-L1脂肪细胞的分化过程中。 我们看了 gadd 153（其编码C/EBP相关蛋白， 缺乏功能性DNA结合结构域）、C/EBP α和GLUT 4，并发现 C/EBP和GLUT 4的mRNA水平之间的关联， 的文化条件。 然而，gadd 153的水平似乎 mRNA与C/EBP α不同，这取决于葡萄糖水平 在培养基中。