Glucose-induced sympathetic activity and energy expenditure during acute alpha2-adrenergic antagonism in obese subjects.
OBJECTIVE
To determine the effect of an alpha2-adrenoceptor antagonist, idazoxan, on the sympathetic nervous system and on energy expenditure responses after an oral glucose load, in obese patients. (idazoxan acts as an indirect sympathomimetic drug through blockade of presynaptic alpha2-adrenoceptors).


METHODS
Double-blind randomized placebo-controlled cross-over study. Idazoxan (40 mg) or placebo were administered orally 90 min before a 100 g oral glucose load.


METHODS
Twelve long-standing obese subjects (six men and six women, age range from 24 to 45 y, body mass index range from 30.2 to 41.3 kg/m2).


METHODS
Energy expenditure was derived from oxygen consumption and carbon dioxide production according to indirect calorimetry. Plasma samples were obtained for plasma adrenaline and noradrenaline, glucose, non-esterified fatty acid (NEFA), glycerol and insulin determinations.


RESULTS
The plasma noradrenaline concentration response to the glucose load was significantly higher after idazoxan than after placebo administration. The time-course of glucose load-induced thermogenesis was not significantly different after administration of idazoxan nor placebo. Idazoxan administration did not modify the insulin, non-esterified fatty acids or glycerol concentration responses to the glucose load. Neither heart rate nor blood pressure values were modified by idazoxan when compared to placebo. However, idazoxan significantly improved glucose tolerance.


CONCLUSIONS
The alpha2-adrenergic antagonist idazoxan increases glucose-induced sympathetic activity but not energy expenditure in obese subjects. These data do not argue for the development of alpha2AR antagonist compounds as anti-obesity treatment.
Thalamas
C
C
INSERM U-317 and the Centre d'Investigation Clinique Centre Hospitalier Universitaire, Toulouse, France.
Galitzky
J
J
Sénard
J M
JM
Lafontan
M
M
Montastruc
J L
JL
Berlan
M
M
Barbe
P
P
D000317:Adrenergic alpha-Antagonists; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D019329:Idazoxan; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D009765:Obesity / Q000503:physiopathology*; D010101:Oxygen Consumption; D010919:Placebos; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D000317:Adrenergic alpha-Antagonists; D005230:Fatty Acids, Nonesterified; D010919:Placebos; D011942:Receptors, Adrenergic, alpha; D005947:Glucose; D009638:Norepinephrine; D019329:Idazoxan