GLUCOSE SIGNALING AND REGULATION OF GENE EXPRESSION IN 3T3-L1 ADIPOCYTES

工作概述：有大量证据支持这一概念 葡萄糖毒性，其中高血糖症导致 胰腺分泌胰岛素和外周血胰岛素作用 组织（例如，脂肪、心脏和骨骼肌）。 这种抵抗 胰岛素作用与葡萄糖代谢增加有关 通过己糖胺生物合成途径。 高的影响 葡萄糖和葡萄糖代谢产物的浓度对 对于调节脂肪细胞功能重要的基因仍然主要是 未知 这项研究是为了看看监管的 转录因子CCAAT/增强子结合蛋白（C/EBP）α 葡萄糖和葡糖胺，一种己糖胺途径的产物， 培养的脂肪细胞系，已知其对 胰岛素 这种转录因子与 脂肪细胞能量稳态建立和维持 控制几种基因产物的表达，包括 胰岛素反应性葡萄糖转运蛋白GLUT 4，脂质合成酶， 和瘦素。 瘦素仅在脂肪细胞中表达， 被认为是调节体重的一种激素 通过控制食欲和能量消耗。 我们最初 结果表明，转录和mRNA积累的减少， 高浓度葡萄糖引起的C/EBP-α基因突变， 葡萄糖胺伴随着表达的成比例减少， GLUT4基因。 稳定表达启动子的一部分， 与报告基因融合的C/EBP-α基因已经证明启动子 这些处理降低了活性。 现在人们认识到， 脂肪组织除了具有作为内分泌系统的功能外， 一个能量储存库 一项旨在评估 高血糖和葡萄糖胺输注对脂肪细胞代谢和 大鼠的内分泌功能正在进行中。我们在了解 调节脂肪细胞生理学的因素应允许 肥胖相关胰岛素抵抗的有效干预措施， 在美国和其他西方国家， 社会。

Summary of work: There is a large body of evidence supporting the concept of glucose toxicity, in which hyperglycemia causes the deterioration of insulin secretion from the pancreas and insulin action in peripheral tissues (e.g., adipose, heart and skeletal muscle). This resistance to insulin action has been linked to an increase in glucose metabolism through the hexosamine biosynthetic pathway. The effect of high concentrations of glucose and glucose metabolites on the expression of genes important for regulation of adipose cell functions remains largely unknown. This study was undertaken to look at the regulation of the transcription factor CCAAT/enhancer-binding protein (C/EBP) alpha by glucose and glucosamine, a product of the hexosamine pathway, in a cultured adipose cell line that is known for its high responsiveness to insulin. This transcription factor has been implicated in the establishment and maintenance of energy homeostasis in adipocytes by controlling the expression of several gene products which includes the insulin-responsive glucose transporter GLUT4, lipid-synthesizing enzymes, and leptin. Leptin is exclusively expressed in adipocytes and is considered as a hormone that acts centrally to regulate body weight through the control of appetite and energy expenditure. Our initial results indicate that the decrease in transcription and mRNA accumulation of C/EBP-alpha gene caused by high concentrations of glucose or glucosamine is accompanied by a proportional reduction in the expression of GLUT4 gene. Stable expression of a portion of the promoter for C/EBP-alpha gene fused to a reporter gene has demonstrated that promoter activity was decreased by these treatments. It is now recognized that the adipose tissue plays major endocrine roles in addition to its function as an energy storage depot. A study aimed at evaluating the effect of hyperglycemia and glucosamine infusion on adipocyte metabolic and endocrine functions in rats is underway. Progress in our understanding of factors regulating adipose cell physiology shall allow the development of effective interventions for obesity-related insulin resistance, a major contributor to morbidity and mortality in the U.S. and other Western societies.