1.Alterations of epinephrine-induced gluconeogenesis in aging.
Kyungtae KIM ; Sung Chun CHO ; Anthony COVA ; Ik Soon JANG ; Sang Chul PARK
Experimental & Molecular Medicine 2009;41(5):334-340
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.
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
2.Alterations of epinephrine-induced gluconeogenesis in aging.
Kyungtae KIM ; Sung Chun CHO ; Anthony COVA ; Ik Soon JANG ; Sang Chul PARK
Experimental & Molecular Medicine 2009;41(5):334-340
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.
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