title: Remodeling of hepatic metabolism and hyperaminoacidemia in mice deficient in proglucagon-derived peptides.
abstract: Glucagon is believed to be one of the most important peptides for upregulating blood glucose levels. However, homozygous glucagon-green fluorescent protein (gfp) knock-in mice (Gcg(gfp/gfp): GCGKO) are normoglycemic despite the absence of proglucagon-derived peptides, including glucagon. To characterize metabolism in the GCGKO mice, we analyzed gene expression and metabolome in the liver. The expression of genes encoding rate-limiting enzymes for gluconeogenesis was only marginally altered. On the other hand, genes encoding enzymes involved in conversion of amino acids to metabolites available for the tricarboxylic acid cycle and/or gluconeogenesis showed lower expression in the GCGKO liver. The expression of genes involved in the metabolism of fatty acids and nicotinamide was also altered. Concentrations of the metabolites in the GCGKO liver were altered in manners concordant with alteration in the gene expression patterns, and the plasma concentrations of amino acids were elevated in the GCGKO mice. The insulin concentration in serum and phosphorylation of Akt protein kinase in liver were reduced in GCGKO mice. These results indicated that proglucagon-derived peptides should play important roles in regulating various metabolic pathways, especially that of amino acids. Serum insulin concentration is lowered to compensate the impacts of absent proglucagon-derived peptide on glucose metabolism. On the other hand, impacts on other metabolic pathways are only partially compensated by reduced insulin action.
authors.affiliation: Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Watanabe
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seino
authors.forename: Hiroki
authors.initials: H
authors.lastname: Miyahira
authors.forename: Michiyo
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Ayako
authors.initials: A
authors.lastname: Fukami
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Takagishi
authors.forename: Jun
authors.initials: J
authors.lastname: Sato
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fukuwatari
authors.forename: Katsumi
authors.initials: K
authors.lastname: Shibata
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Murata
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000596:Amino Acids / Q000097:blood* / Q000378:metabolism; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052336:Proglucagon / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000596:Amino Acids; D010446:Peptide Fragments; D049452:Green Fluorescent Proteins; D052336:Proglucagon