title: Alterations of epinephrine-induced gluconeogenesis in aging.
abstract: The effects of glucagon and epinephrine on gluconeogenesis in young (4 month) and old (24 month) Fisher 344 rat hepatocytes were compared. In contrast to glucagon, which had a similar effect on gluconeogenesis in both young and old cells, epinephrine caused a smaller increase in gluconeogenesis in old rat hepatocytes than in young hepatocytes. beta2 adrenergic receptor (beta2-AR) expression slightly decreased in aged rat liver, and there were differences between young and old hepatocytes in their patterns of G protein coupled receptor kinases, which are involved in the activation of beta2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of beta-arrestin, which is recruited by the phosphorylated beta2-AR for internalization and degradation, increased in aged rat liver. GRK3 overexpression also decreased the glucose output from young rat hepatocytes. We conclude that an age-associated reduction in epinephrine-induced gluconeogenesis occurs through the epinephrine receptor desensitizing system.
authors.affiliation: Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University, Korea.
authors.forename: Kyungtae
authors.initials: K
authors.lastname: Kim
authors.forename: Sung Chun
authors.initials: SC
authors.lastname: Cho
authors.forename: Anthony
authors.initials: A
authors.lastname: Cova
authors.forename: Ik Soon
authors.initials: IS
authors.lastname: Jang
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects*; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000378:metabolism; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D008297:Male; D008954:Models, Biological; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D018343:Receptors, Adrenergic, beta-2; D005934:Glucagon; D054770:G-Protein-Coupled Receptor Kinase 3; D054769:G-Protein-Coupled Receptor Kinase 2; D004837:Epinephrine