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Activation of ₂-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men

¹Department of Sports Medicine, Third Faculty of Medicine, Charles University, ²Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; ³Obesity Research Unit, Institut National de la Santé et de la Recherche Médicale, Unité 586, and ⁴Department of Medical and Clinical Pharmacology, Faculty of Medicine, 31073 Toulouse, France

Submitted 14 November 2002 ; accepted in final form 21 May 2003

The 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 ± 0.9 yr; body mass index: 23.8 ± 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 µM) or epinephrine (1 and 10 µM) 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 µM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 µM)-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 µM phentolamine (a nonselective -AR antagonist), the inhibition of epinephrine (10 µM)-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

This article has been cited by other articles:

				C. Moro, J. Galitzky, C. Sengenes, F. Crampes, M. Lafontan, and M. Berlan Functional and Pharmacological Characterization of the Natriuretic Peptide-Dependent Lipolytic Pathway in Human Fat Cells J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 984 - 992. [Abstract] [Full Text] [PDF]