Alterations of epinephrine-induced gluconeogenesis in aging.
10.3858/emm.2009.41.5.037
- Author:
Kyungtae KIM
1
;
Sung Chun CHO
;
Anthony COVA
;
Ik Soon JANG
;
Sang Chul PARK
Author Information
1. Department of Biochemistry and Molecular Biology, The Aging and Apoptosis Research Center, Seoul National University, College of Medicine, Seoul 110-799, Korea. scpark@snu.ac.kr
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
aging;
epinephrine;
glucagon;
gluconeogenesis;
G-protein-coupled receptor kinases;
hepatocytes
- MeSH:
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
- From:Experimental & Molecular Medicine
2009;41(5):334-340
- CountryRepublic of Korea
- Language:English
-
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.
