REGULATION OF GLUCOSE TRANSPORTER GENE EXPRESSION

GLUT4葡萄糖转运体是肌肉中表达的主要亚型， 脂肪组织，这两种组织类型主要负责 维持全身葡萄糖动态平衡。GLUT4亚型扮演着一个 在这一过程中的关键作用是促进葡萄糖在这些细胞中的吸收 组织对胰岛素刺激的反应。GLUT4葡萄糖的调节 传输器功能在多个级别上发生，其中几个级别 与胰岛素抵抗和糖尿病有关。例如，多个 研究证明，GLUT4在以下状态下表达减少 胰岛素缺乏性糖尿病和空腹。进一步的患者研究表明 提示脂肪组织中GLUT4的表达与NIDDM相关。 最近，组织特异性模式以及 GLUT4表达的激素/代谢调节已被证明发生 在转录水平上。 基于GLUT4基因在病理生理学中的中心作用 与糖尿病有关，我们已经提出了一系列研究来解决 该基因的组织特异性和荷尔蒙/代谢调节。这个 参与GLUT4基因调控的基本分子事件明显 对于我们理解脂肪和脂肪的重要问题 肌肉特异性基因调控以及对葡萄糖的控制 动态平衡、新陈代谢和能量生产。因此，我们计划 继续我们的研究，描绘出导致 胰岛素的激素/代谢和组织特异性调节- 反应性GLUT4基因。这将通过详细分析 GLUT4启动子功能及其顺式DNA调控元件的鉴定 使用几种互补的方法。然后，这些研究将允许 组织特异性DNA结合因子的鉴定与分离 负责荷尔蒙/代谢(胰岛素缺乏性糖尿病和 禁食/再进食状态)和特定组织(白色脂肪、棕色 脂肪、心肌和骨骼肌)对该基因的调控。

The GLUT4 glucose transporter is the major isoform expressed in muscle and adipose tissue, the two tissue types primarily responsible for the maintenance of whole body glucose homeostasis. The GLUT4 isoform plays a key role in this process by facilitating the uptake of glucose in these tissues in response to insulin stimulation. Regulation of GLUT4 glucose transporter functions occurs at multiple levels, several of which are associated with insulin resistance and diabetes. For example, multiple studies have documented that GLUT4 expression is decreased in states of insulin-deficient diabetes and fasting. Further patient studies have suggested a correlation in adipose tissue expression of GLUT4 with NIDDM. More recently, both the tissue-specific pattern as well as the hormonal/metabolic regulation of GLUT4 expression have been shown to occur at the transcriptional level. Based upon the central role of the GLUT4 gene in the pathophysiology associated with diabetes, we have proposed a series of studies to address the tissue-specific and hormonal/metabolic regulation of this gene. The basic molecular events involved in GLUT4 gene regulation are clearly important issues which are necessary for our understanding of adipose and muscle-specific gene regulation as well as for the control of glucose homeostasis, metabolism and energy production. We therefore plan to continue our studies delineating the molecular mechanisms responsible for the hormonal/metabolic and tissue-specific regulation of the insulin- responsive GLUT4 gene. This will be accomplished by detailed analysis of GLUT4 promoter function and identification of cis-DNA regulatory elements using several complementary approaches. These studies will then allow for the characterization and isolation of tissue-specific DNA binding factors responsible for the hormonal/metabolic (insulin-deficient diabetes and fasting/refeeding states) and tissue-specific (white adipose, brown adipose, cardiac and skeletal muscle) regulation of this gene.