Regulation of Glucose Homeostasis and Lipid Metabolism by PPP1R3G-mediated Hepatic Glycogenesis

被引：42

作者：

Zhang, Yongxian ^{[1
]}

Xu, Daqian ^{[1
]}

Huang, Heng ^{[1
]}

Chen, Susie ^{[1
]}

Wang, Lingdi ^{[1
]}

Zhu, Lu ^{[1
]}

Jiang, Xiaomeng ^{[1
]}

Ruan, Xiangbo ^{[1
]}

Luo, Xiaolin ^{[1
]}

Cao, Peijuan ^{[1
]}

Liu, Weizhong ^{[1
]}

Pan, Yi ^{[1
]}

Wang, Zhenzhen ^{[1
]}

Chen, Yan ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci,Grad Sch, Shanghai 200031, Peoples R China

来源：

MOLECULAR ENDOCRINOLOGY | 2014年 / 28卷 / 01期

基金：

中国国家自然科学基金;

关键词：

PROTEIN PHOSPHATASE 1; TARGETING SUBUNIT; INSULIN-RESISTANCE; LIVER; MUSCLE; SYNTHASE; PHOSPHORYLATION; IDENTIFICATION; BINDING; KINASE;

D O I：

10.1210/me.2013-1268

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Liver glycogen metabolism plays an important role in glucose homeostasis. Glycogen synthesis is mainly regulated by glycogen synthase that is dephosphorylated and activated by protein phosphatase 1 (PP1) in combination with glycogen-targeting subunits or G subunits. There are seven G subunits (PPP1R3A to G) that control glycogenesis in different organs. PPP1R3G is a recently discovered G subunit whose expression is changed along the fasting-feeding cycle and is proposed to play a role in postprandial glucose homeostasis. In this study, we analyzed the physiological function of PPP1R3G using a mouse model with liver-specific overexpression of PPP1R3G. PPP1R3G overexpression increases hepatic glycogen accumulation, stimulates glycogen synthase activity, elevates fasting blood glucose level, and accelerates postprandial blood glucose clearance. In addition, the transgenic mice have a reduced fat composition, together with decreased hepatic triglyceride level. Fasting-induced hepatic steatosis is relieved by PPP1R3G overexpression. In addition, PPP1R3G overexpression is able to elevate glycogenesis in primary hepatocytes. The glycogen-binding domain is indispensable for the physiological activities of PPP1R3G on glucose metabolism and triglyceride accumulation in the liver. Cumulatively, these data indicate that PPP1R3G plays a critical role in postprandial glucose homeostasis and liver triglyceride metabolism via its regulation on hepatic glycogenesis.

引用

页码：116 / 126

页数：11

共 36 条

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