Russell Steven Thomas, Tisdale Michael John
Nutritional Biomedicine, School of Health Sciences, Aston University, Birmingham B4 7ET, UK.
Biochim Biophys Acta. 2012 Apr;1821(4):590-9. doi: 10.1016/j.bbalip.2011.12.003. Epub 2011 Dec 23.
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).
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.
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.
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.
本研究的目的是确定β-肾上腺素能受体（β-AR）是否在锌-α2-糖蛋白（ZAG）的抗肥胖和抗糖尿病作用中发挥作用。
已在转染了人β1-、β2-、β3-AR的CHO-K1细胞和ob/ob小鼠中对此进行了研究。进行了环磷酸腺苷（cAMP）测定以及结合研究。用ZAG处理ob/ob小鼠，并在有或没有普萘洛尔的情况下检测葡萄糖转运和胰岛素情况。
ZAG与β3-AR的结合亲和力（解离常数Kd为46±1nM）高于β2-AR（Kd为71±3nM），而与β1-AR无结合，这与用ZAG处理的转染了各种β-AR的CHO-K1细胞中环磷酸腺苷的增加相关。用ZAG处理ob/ob小鼠可增加腓肠肌、白色和棕色脂肪组织中β3-AR的蛋白表达，但对β1-和β2-AR的表达无影响。体重减轻，口服葡萄糖耐量试验中尿葡萄糖排泄减少、体温升高、最大血浆葡萄糖和胰岛素水平降低，以及骨骼肌和脂肪组织中葡萄糖转运的刺激作用，均被非特异性β-AR拮抗剂普萘洛尔完全减弱。
结果表明，ZAG对ob/ob小鼠体重和胰岛素敏感性的影响是通过β-3AR或可能通过β2-AR表现出来的。
