Alterations of epinephrine-induced gluconeogenesis in aging

Exp Mol Med. 2009 May 31;41(5):334-40. doi: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists
  • 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 / metabolism

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Glucagon
  • G-Protein-Coupled Receptor Kinase 3
  • G-Protein-Coupled Receptor Kinase 2
  • Epinephrine