Alterations of epinephrine-induced gluconeogenesis in aging.
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.
Kim
Kyungtae
K
Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University, Korea.
Cho
Sung Chun
SC
Cova
Anthony
A
Jang
Ik Soon
IS
Park
Sang Chul
SC
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
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