title: Fasting-induced protein phosphatase 1 regulatory subunit contributes to postprandial blood glucose homeostasis via regulation of hepatic glycogenesis.
abstract: OBJECTIVE
  Most animals experience fasting-feeding cycles throughout their lives. It is well known that the liver plays a central role in regulating glycogen metabolism. However, how hepatic glycogenesis is coordinated with the fasting-feeding cycle to control postprandial glucose homeostasis remains largely unknown. This study determines the molecular mechanism underlying the coupling of hepatic glycogenesis with the fasting-feeding cycle.
  
  
  METHODS
  Through a series of molecular, cellular, and animal studies, we investigated how PPP1R3G, a glycogen-targeting regulatory subunit of protein phosphatase 1 (PP1), is implicated in regulating hepatic glycogenesis and glucose homeostasis in a manner tightly orchestrated with the fasting-feeding cycle.
  
  
  RESULTS
  PPP1R3G in the liver is upregulated during fasting and downregulated after feeding. PPP1R3G associates with glycogen pellet, interacts with the catalytic subunit of PP1, and regulates glycogen synthase (GS) activity. Fasting glucose level is reduced when PPP1R3G is overexpressed in the liver. Hepatic knockdown of PPP1R3G reduces postprandial elevation of GS activity, decreases postprandial accumulation of liver glycogen, and decelerates postprandial clearance of blood glucose. Other glycogen-targeting regulatory subunits of PP1, such as PPP1R3B, PPP1R3C, and PPP1R3D, are downregulated by fasting and increased by feeding in the liver.
  
  
  CONCLUSIONS
  We propose that the opposite expression pattern of PPP1R3G versus other PP1 regulatory subunits comprise an intricate regulatory machinery to control hepatic glycogenesis during the fasting-feeding cycle. Because of its unique expression pattern, PPP1R3G plays a major role to control postprandial glucose homeostasis during the fasting-feeding transition via its regulation on liver glycogenesis.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Luo
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Ruan
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Jiang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhu
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Ding
authors.forename: Weizhong
authors.initials: W
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Pan
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005215:Fasting / Q000097:blood* / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019518:Postprandial Period; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D008112:Liver Glycogen; C000591005:PPP1R3G protein, mouse; D054645:Protein Phosphatase 1