Overexpression of β2-adrenergic receptors in mouse liver alters the expression of gluconeogenic and glycolytic enzymes

被引:25
|
作者
Erraji-Benchekroun, L
Couton, D
Postic, C
Borde, I
Gaston, J
Guillet, JG
André, C
机构
[1] CNRS, UMR 8104, INSERM, U567,Inst Cochin,Dept Immunol, F-75014 Paris, France
[2] CNRS, UMR 8104, INSERM, U567,Inst Cochin,Dept Genet Dev & Mol Pathol, F-75014 Paris, France
[3] CNRS, UMR 8104, INSERM, U567,Inst Cochin,Dept Endocrinol, F-75014 Paris, France
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2005年 / 288卷 / 04期
关键词
beta-adrenergic receptor; glycogen; glucose; phosphoenolpyruvate carboxykinase; L-pyruvate kinase;
D O I
10.1152/ajpendo.00113.2004
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the livers of humans and many other mammalian species, beta(2)-adrenergic receptors (beta(2)-ARs) play an important role in the modulation of glucose production by glycogenolysis and gluconeogenesis. In male mice and rats, however, the expression and physiological role of hepatic beta(2)-ARs are rapidly lost with development under normal physiological conditions. We previously described a line of transgenic mice, F28 (Andre C, Erraji L, Gaston J, Grimber G, Briand P, and Guillet JG. Eur J Biochem 241: 417-424, 1996), which carry the human beta(2)-AR gene under the control of its own promoter. In these mice, hepatic beta(2)-AR levels are shown to increase rapidly after birth and, as in humans, be maintained at an elevated level in adulthood. F28 mice display strongly enhanced adenylyl cyclase responses to beta-AR agonists in their livers and, compared with normal mice, have increased basal hepatic adenylyl cyclase activity. In this report we demonstrate that, under normal physiological conditions, this increased beta(2)-AR activity affects the expression of the gluconeogenic and glycolytic key enzymes phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and L-pyruvate kinase and considerably decreases hepatic glycogen levels. Furthermore, we show that the effects of beta-adrenergic ligands on liver glycogen observed in humans are reproduced in these mice: liver glycogen levels are strongly decreased by the beta(2)-AR agonist clenbuterol and increased by the beta-AR antagonist propranolol. These transgenic mice open new perspectives for studying in vivo the hepatic beta(2)-AR system physiopathology and for testing the effects of beta-AR ligands on liver metabolism.
引用
收藏
页码:E715 / E722
页数:8
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