Activation of alpha(2)-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men
Abstract
The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha(2)-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemic-hyperinsulinemic clamp and in control conditions.
Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 muM) or epinephrine (1 and 10 muM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent 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 muM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 muM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals.
When epinephrine was infused in combination with 100 muM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 muM)-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 beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha(2)-ARs.