INSULIN REGULATION OF G6PDH

描述(摘自申请者的摘要)：胰岛素调节 参与多种代谢过程的多种基因的表达。 旨在了解胰岛素对基因表达调控的研究已经 重点介绍糖酵解、糖异生、糖原和脂肪中的关键酶 酸合成。到目前为止，还没有涉及到的共同因素 已经找到了规则。与广泛的刻画不同的是 已经在糖酵解、糖异生、 在糖原和脂肪酸的合成方面，关于 磷酸戊糖途径。这条路径可以被认为是在 碳水化合物和脂肪代谢的界面不仅是 碳水化合物的代谢，但也NADPH是为了生物合成 脂肪酸。在肝脏中，胰岛素诱导合成 葡萄糖-6-磷酸脱氢酶(G6PDH)是细胞周期中的关键限速酶 磷酸戊糖途径。 因此，了解G6PDH被调控的机制是 重要的是不仅要了解碳水化合物的调节 而且还有脂肪酸新陈代谢。我们假设G6PDH是一个理想的模型 研究胰岛素对两种代谢途径均有抑制作用。详细研究 因此，胰岛素对该酶基因的调节可能导致 更好地理解碳水化合物和蛋白质的协调控制 脂肪酸代谢，这对于我们理解 代谢紊乱，如心血管疾病和糖尿病。AS 在以下具体目标中概述了这项提案的目标是 系统地描述和确定胰岛素的作用机制 调节G6PDH的表达。为了做到这一点，调查人员 我将首先描述G6PDH诱导所需的DNA序列 用胰岛素治疗。然后，研究人员将确定蛋白质因素的特征(S) 它与DNA结合，并且是这种增加的 吉恩。

DESCRIPTION (Adapted from applicant's abstract): Insulin regulates the expression of many genes involved in a variety of metabolic processes. Studies aimed at understanding insulin regulation of gene expression have focused on key enzymes in glycolysis, gluconeogenesis, glycogen and fatty acid synthesis. To date, no common element that is involved in this regulation has been found. Unlike the extensive characterization that has been done on the expression of enzymes for glycolysis, gluconeogenesis, glycogen and fatty acid synthesis, little has been done with respect to the pentose phosphate pathway. This pathway can be considered to be at the interface of carbohydrate and lipid metabolism in that not only is carbohydrate metabolized but also NADPH is produced for the biosynthesis of fatty acids. In the liver, insulin, induces the synthesis of glucose-6-phosphate dehydrogenase (G6PDH), the key rate-limiting enzyme in the pentose phosphate pathway. Understanding the mechanism by which G6PDH is regulated is therefore of major importance in understanding not only the regulation of carbohydrate but also fatty acid metabolism. We hypothesize that G6PDH is an ideal model to study ho insulin can attenuate both metabolic pathways. Detailed studies of insulin regulation of the gene for this enzyme may therefore lead to a better understanding of the coordinate control of both carbohydrate and fatty acid metabolism and this is critical for our understanding of metabolic disorders such as cardiovascular disease and diabetes. As outlined in the following specific aims, the goal of this proposal is to systematically delineate and determine the mechanism by which insulin regulates the expression of G6PDH. To accomplish this, the investigators will first delineate the DNA sequences that are required for G6PDH induction by insulin. The investigators will then characterize the protein factor(s) that bind the DNA and are required for this increased expression of the gene.