项目名称

外周组织调控血糖代谢稳态的作用机制

学科学类

H07 医学科学部_内分泌系统/代谢和营养支持

项目批准号

81390353

资助类型

重大项目

资助经费

540万元

项目负责人

陈雁

职称

研究员

批准年份

2013

单位名称

中国科学院上海生命科学研究院

起止时间

2014-01至2018-12

项目中文摘要

在2型糖尿病的病理生理过程中，外周组织如肝脏和脂肪对于糖稳态平衡的维持发挥了关键作用。肝脏是机体一个最主要的代谢器官，肝脏糖原代谢参与了餐后血糖的稳态平衡调控。脂肪组织是能量的主要储备器官，同时也能分泌脂肪细胞因子参与机体的糖脂代谢和能量平衡，而白色脂肪向棕色脂肪的转化过程对于机体能量代谢和糖代谢具有重要的调控功能。本课题将以肝脏和脂肪组织为主要研究方向，深入揭示外周组织在调控血糖稳态中的关键功能，包括阐明PPP1R3G在肝糖原代谢过程中的关键生物学和生理学功能、及其对于餐后血糖代谢的调控功能，揭示一个脂肪细胞因子脂联素受体家族成员PAQR3参与胰岛素信号通路和胰岛素抵抗的调控功能，并探索白色脂肪转分化为棕色脂肪和机制和作用靶点及其对于糖稳态平衡的调控功能。这些研究不但能加深对于外周组织对于糖代谢稳态平衡的调节机制，并且能够为未来有效地控制2型糖尿病的发生发展提供新的干预措施和靶点。

项目英文摘要

It is well known that peripheral tissues such as liver and adipose plays critical roles during the pathophysiological process of type 2 diabetes. Liver is the paramount tissue involved in different areas of metabolism. Glycogen metabolism of the liver is actively involved in maintaining glucose homeostasis during difference phases of the feeding and fasting cycle. On the other hand, adipose tissue is not only a major organ in energy reservation, but also actively involved in glucose and lipid metabolism via secretion of adipokines such as adiponectin. In addition, the trans-differentiation of white adipose tissue to the brown fat is implicated in the regulation of energy metabolism as well as glucose metabolism. This proposal is aimed to address the unique roles of liver and adipose tissue in the control of glucose homeostasis. In particular, we will investigate the functional roles of PPP1R3G, a critical molecule involved in hepatic glycogen metabolism, in the maintenance of blood glucose homeostasis during the fasting/feeding cycle. We will also analyze how PAQR3, a member of the adiponectin receptor family that regulates cell signaling via altering compartmentalization, is involved in the regulation of insulin signaling and insulin resistance. In addition, we will analyze how trans-differentiation of white adipose tissue to brown fat is involved in energy and glucose metabolism. In conclusion, these studies will provide new insights about how peripheral tissues are involved in the regulation of glucose homeostasis. Furthermore, these studies will provide new strategies and potential therapeutic targets for the treatment of type 2 diabetes in the future.

结题摘要

在2型糖尿病的病理生理过程中，外周组织如肝脏和脂肪对于糖稳态平衡的维持发挥了关键作用。肝脏是机体一个最主要的代谢器官，肝脏糖原代谢参与了餐后血糖的稳态平衡调控。脂肪组织是能量的主要储备器官，同时也能分泌脂肪细胞因子参与机体的糖脂代谢和能量平衡，而白色脂肪向棕色脂肪的转化过程对于机体能量代谢和糖代谢具有重要的调控功能。本课题以肝脏和脂肪组织为主要研究方向，深入揭示了外周组织在调控血糖稳态中的关键功能。通过课题的实施，阐明了PPP1R3G在肝糖原代谢过程中的关键生物学和生理学功能及其对于糖脂稳态的调控功能，揭示了脂联素受体家族成员PAQR3参与糖脂稳态的调控功能，探索了白色脂肪转分化为棕色脂肪和机制和作用靶点及其对于糖稳态平衡的调控功能，并进行了一系列营养干预实验揭示了间歇性节食和肠道菌群对糖尿病的干预作用。这些研究加深了对于外周组织对于糖代谢稳态平衡的调节机制，为未来有效地控制2型糖尿病的发生发展提供新的干预措施和靶点。受项目资助共发表文章41篇，申请专利4项，培养毕业研究生40人。

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