Alterations of epinephrine-induced gluconeogenesis in aging |
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Authors: | Kyungtae Kim Sung Chun Cho Anthony Cova Ik Soon Jang Sang Chul Park |
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Affiliation: | 1Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University, College of Medicine, Seoul 110-799, Korea.;2National Cancer Center, Goyang 410-769, Korea.;3Korea Basic Science Institute, Daejeon 305-333, Korea. |
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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. β2 adrenergic receptor (β2-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 β2-AR receptor signal desensitization. The major isoform of the kinase changed from GRK2 to GRK3 and the expression of β-arrestin, which is recruited by the phosphorylated β2-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. |
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Keywords: | aging epinephrine glucagon gluconeogenesis G-protein-coupled receptor kinases hepatocytes |
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