Remodeling of Hepatic Metabolism and Hyperaminoacidemia in Mice Deficient in Proglucagon-Derived Peptides
| Autor: | Katsumi Shibata, Jun Sato, Yoshitaka Hayashi, Hiroki Miyahira, Yutaka Oiso, Yoshiko Takagishi, Michiyo Yamamoto, Chika Watanabe, Ayako Fukami, Tsutomu Fukuwatari, Nobuaki Ozaki, Yoshiharu Murata, Yusuke Seino |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism Green Fluorescent Proteins Carbohydrate metabolism Biology Proglucagon Models Biological Glucagon Gene Expression Regulation Enzymologic Mice Metabolic Diseases Internal medicine Internal Medicine medicine Animals Amino Acids Mice Knockout chemistry.chemical_classification Metabolism Lipid Metabolism medicine.disease Peptide Fragments Up-Regulation Amino acid Mice Inbred C57BL Metabolic pathway Endocrinology Liver Biochemistry chemistry Gluconeogenesis Hyperaminoacidemia Metabolic Networks and Pathways |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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 (Gcggfp/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. |
| Databáze: | OpenAIRE |
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