title: Metabolic impact of overexpression of liver glycogen synthase with serine-to-alanine substitutions in rat primary hepatocytes.
abstract: To investigate the effect of elevation of liver glycogen synthase (GYS2) activity on glucose and glycogen metabolism, we performed adenoviral overexpression of the mutant GYS2 with six serine-to-alanine substitutions in rat primary hepatocytes. Cell-free assays demonstrated that the serine-to-alanine substitutions caused constitutive activity and electrophoretic mobility shift. In rat primary hepatocytes, overexpression of the mutant GYS2 significantly reduced glucose production by 40% and dramatically induced glycogen synthesis via the indirect pathway rather than the direct pathway. Thus, we conclude that elevation of glycogen synthase activity has an inhibitory effect on glucose production in hepatocytes by shunting gluconeogenic precursors into glycogen. In addition, although intracellular compartmentation of glucose-6-phosphate (G6P) remains unclear in hepatocytes, our results imply that there are at least two G6P pools via gluconeogenesis and due to glucose phosphorylation, and that G6P via gluconeogenesis is preferentially used for glycogen synthesis in hepatocytes.
authors: Tsukuba Research Institute, Banyu Pharmaceutical Co Ltd, 3 Okubo, Tsukuba, Ibaraki, Japan.
authors: Akito
authors: A
authors: Kadotani
authors: Maho
authors: M
authors: Fujimura
authors: Takao
authors: T
authors: Nakamura
authors: Sumika
authors: S
authors: Ohyama
authors: Naomoto
authors: N
authors: Harada
authors: Hiroko
authors: H
authors: Maruki
authors: Yoshitaka
authors: Y
authors: Tamai
authors: Akio
authors: A
authors: Kanatani
authors: Jun-Ichi
authors: J
authors: Eiki
authors: Yasufumi
authors: Y
authors: Nagata
mesh_terms: D000409:Alanine / Q000235:genetics*; D019943:Amino Acid Substitution; D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000096:biosynthesis; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006006:Glycogen Synthase / Q000096:biosynthesis* / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012694:Serine / Q000235:genetics*
chemical_list: D012694:Serine; D019298:Glucose-6-Phosphate; D006003:Glycogen; D006006:Glycogen Synthase; D005947:Glucose; D000409:Alanine