Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG).
OBJECTIVE
The goal of the current study is to determine whether the β-adrenoreceptor (β-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotein (ZAG).


METHODS
This has been investigated in CHO-K1 cells transfected with the human β1-, β2-, β3-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 β3-AR with higher affinity (Kd 46±1nM) than the β2-AR (Kd 71±3nM) while there was no binding to the β1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various β-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of β3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of β1- and β2-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 β-AR antagonist propranolol.


CONCLUSIONS
The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a β-3AR, or possibly a β2-AR.
Nutritional Biomedicine, School of Health Sciences, Aston University, Birmingham B4 7ET, UK. s.t.russell1@aston.ac.uk
Steven Thomas
ST
Russell
Michael John
MJ
Tisdale
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control; D011433:Propranolol / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D029589:Seminal Plasma Proteins / Q000378:metabolism* / Q000494:pharmacology; D000090203:Zn-Alpha-2-Glycoprotein
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein; D011433:Propranolol