2型糖尿病已逐步成为严重危害国民健康并阻挠我国经济发展的一个重要疾病，而糖代谢稳态失衡是2型糖尿病最基本的病理生理学改变，对于糖代谢稳态失衡的深入研究将极大加深对于2型糖尿病致病机理的理解。本项目针对糖代谢稳态失衡的发生和发展为研究核心，根据国际该领域的研究热点提出创新性科学假说，组织跨学科的联合力量共同攻关，将有助于从多个角度阐明糖代谢稳态维持和失衡的机制。本项目设置了4 个课题，分别探讨（1）糖代谢稳态调节基因的转录及转录后调控机制；（2）胰岛β细胞量、胰岛素信号转导调节机制与胰岛素抵抗；（3）外周组织调控血糖代谢稳态的作用机制；（4）代谢性炎症发生的机制及其在糖代谢稳态失衡中的作用。将从分子、细胞、动物等多个层面解析糖代谢稳态失衡的分子机制，阐明多个关键分子在糖代谢稳态维持中的生物学功能，不但能大力提升我国糖代谢研究的水平，也能为未来有效地干预2型糖尿病的发生和发展提供科学依据。

Type 2 diabetes has become a major threat to the public health and economy growth of China. Dysregulation of glucose homeostasis is the most fundamental pathophysiological features of type 2 diabetes and the studies on glucose homeostasis will greatly enhance our understanding about the pathogenesis of type 2 diabetes. This proposal is focused on unraveling the molecular mechanisms underlying the maintenance and dysregulation of glucose homeostasis. A unified strategy to address the key questions of glucose homeostasis is proposed with solid scientific hypotheses based on the state-of-art knowledge on type 2 diabetes. The proposal will be executed to address four specific aims: (1) to analyze transcriptional and posttranscriptional regulation involved in glucose homeostasis; (2) to investigate the roles of beta cell mass, insulin signaling and insulin resistance in the control of glucose metabolism; (3) to study the roles of peripheral tissues such as liver and adipose tissue in the maintenance of glucose homeostasis; (4) to investigate the mechanism of inflammation during the dysregulation of glucose homeostasis. Studies at the levels of molecule, cell, and animals will be utilized to address these specific aims in order to provide a comprehensive understanding about a number of key molecules and pathways involved in the regulation of glucose homeostasis. These studies will not enhance the overall research capability on glucose metabolism in China, but also pave the way for early intervention of type 2 diabetes in the future.