. Activation of ␣2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men. Am J Physiol Endocrinol Metab 285: E599-E607, 2003; 10.1152/ajpendo.00502.2002The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic ␣2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 Ϯ 0.9 yr; body mass index: 23.8 Ϯ 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 M) or epinephrine (1 and 10 M) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dosedependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 M)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 M)-induced lipolysis was significantly greater (by 63 and 70%, P Ͻ 0.01 and P Ͻ 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 M phentolamine (a nonselective ␣-AR antagonist), the inhibition of epinephrine (10 M)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the -adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by ␣2-ARs. microdialysis; glycerol; isoproterenol; blood flow; ␣ 2-adrenergic receptor antagonist NOREPINEPHRINE AND EPINEPHRINE control human adipocyte lipolysis through different adrenergic receptor (AR) subtypes (1,7,20,30). In vitro studies in isolated human fat cells have shown that the activation of ␣ 2 -ARs by epinephrine and norepinephrine impairs the -adrenergic component of catecholamine-induced lipolysis (19,20). In human fat cells, where ␣ 2 -ARs outnumber -ARs, the preferential recruitment of the ␣ 2 -AR at the lowest catecholamine concentrations inhibits lipolysis (20). It is in subcutaneous adipose tissue from both men and women that the strongest ␣ 2 -adrenergic effect has been observed (20, 30). The antilipolytic action of catecholamines in vitro, particularly that of epinephrine (which exhibits a higher affinity for ␣ 2 -AR), is intense in subcutaneous adipocytes from obese subjects (20, 30). Many physiological and pathological studies have shown that the possible deregulation of adrenergic control in adipos...