title: Roles of hepatic glucokinase in intertissue metabolic communication: Examination of novel liver-specific glucokinase knockout mice.
abstract: Glucokinase is expressed principally in pancreatic β-cells and hepatocytes, and catalyzes the phosphorylation of glucose to glucose-6-phosphate, a rate-limiting step of glycolysis. To better understand the roles of hepatic glucokinase, we generated Gck knockout mice by ablating liver-specific exon 1b. The knockout mice exhibited impaired glucose tolerance, decreased hepatic glycogen content, and reduced Pklr and Fas gene expression in the liver, indicating that hepatic glucokinase plays important roles in glucose metabolism. It has also been reported that hepatic glucokinase regulates the expression of thermogenesis-related genes in brown adipose tissue (BAT) and insulin secretion in response to glucose. However, the liver-specific Gck knockout mice displayed neither altered expression of thermogenesis-related genes in BAT nor impaired insulin secretion by β-cells under a normal chow diet. These results suggest that chronic suppression of hepatic glucokinase has a small influence on intertissue (liver-to-BAT as well as liver-to-β-cell) metabolic communication.
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Yamamura Project Laboratory, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Yamamura Project Laboratory, Center for Animal Resources and Development, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamamura
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshizawa
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: k-yamaga@kumamoto-u.ac.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000378:metabolism; D050154:Adiposity; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D005941:Glucokinase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008112:Liver Glycogen / Q000096:biosynthesis; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D008112:Liver Glycogen; D005941:Glucokinase
keywords: Brown adipose tissue; Glucokinase; Glycogen; Insulin secretion; Knockout mouse