Exp Mol Med.  2009 May;41(5):334-340. 10.3858/emm.2009.41.5.037.

Alterations of epinephrine-induced gluconeogenesis in aging

• Kim K
• Cho SC
• Cova A
• Jang IS
• Park SC

• KMID: 1123807
• DOI: http://doi.org/10.3858/emm.2009.41.5.037

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.

Keyword

aging; epinephrine; glucagon; gluconeogenesis; G-protein-coupled receptor kinases; hepatocytes

MeSH Terms

Adrenergic beta-Agonists/*pharmacology
Aging/*drug effects
Animals
Epinephrine/*pharmacology
G-Protein-Coupled Receptor Kinase 2/metabolism
G-Protein-Coupled Receptor Kinase 3/metabolism
Glucagon/pharmacology
*Gluconeogenesis/drug effects
Male
Models, Biological
Phosphorylation
Rats
Rats, Inbred F344
Receptors, Adrenergic, beta-2/agonists/metabolism