Role of 尾-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-伪2-glycoprotien (ZAG)
- 作者：Steven Thomas Russell ; s.t.russell1@aston.ac.uk ; Michael John Tisdale
- 关键词：AUC ; area under the curve ; AMPK ; AMPkinase ; 尾-AR ; beta adrenergic receptor ; BAT ; brown adipose tissue ; CHOK1 ; Chinese hamster ovary cells ; DMEM ; Dulbecco's modified Eagle's medium ; ECL ; enhanced chemiluminescence ; FCS ; foetal calf serum ; LMF ; lipid mobil
- 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
- 出版年：2012
- 期刊代码：18_13881981
- 类别：bio
- 出版时间：April, 2012
- 卷：1821
- 期：4
- 页码：590-599
- 文件大小：1407 K
摘要
Objectives: The goal of the current study is to determine whether the 尾-adrenoreceptor (尾-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-伪2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human 尾1-, 尾2-, 尾3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the 尾3-AR with higher affinity (Kd 46 卤 1 nM) than the 尾2-AR (Kd 71 卤 3 nM) while there was no binding to the 尾1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various 尾-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of 尾3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of 尾1- and 尾2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific 尾-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a 尾-3AR, or possibly a 尾2-AR.