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KMID : 0620920090410050334
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Experimental & Molecular Medicine
2009 Volume.41 No. 5 p.334 ~ p.340
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Alterations of epinephrine-induced gluconeogenesis in aging
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Kim Kyung-Tae
Park Sang-Chul
Cho Sung-Chun
Cova Anthony
Jang Ik-Soon
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Abstract
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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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KEYWORD
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aging, epinephrine, glucagon, gluconeogenesis, G-protein-coupled receptor kinases, hepatocytes
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