Glucose-induced sympathetic activity and energy expenditure during acute α2-adrenergic antagonism in obese subjects

Abstract

OBJECTIVE: To determine the effect of an a 2 -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 a 2 -adrenoceptors). DESIGN: 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. SUBJECTS: 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 kgam 2 ). MEASUREMENTS: 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-esteri®ed fatty acid (NEFA), glycerol and insulin determinations. RESULTS: The plasma noradrenaline concentration response to the glucose load was signi®cantly higher after idazoxan than after placebo administration. The time-course of glucose load-induced thermogenesis was not signi®cantly different after administration of idazoxan nor placebo. Idazoxan administration did not modify the insulin, non-esteri®ed fatty acids or glycerol concentration responses to the glucose load. Neither heart rate nor blood pressure values were modi®ed by idazoxan when compared to placebo. However, idazoxan signi®cantly improved glucose tolerance. CONCLUSION: The a 2 -adrenergic antagonist idazoxan increases glucose-induced sympathetic activity but not energy expenditure in obese subjects. These data do not argue for the development of a a 2 AR antagonist compounds as antiobesity treatment.

Butyrylcholinesterase interactions with amylin may protect pancreatic cells in metabolic syndrome

“…Biochemical and neurophysiological measurements point to enhanced sympathetic and impaired parasympathetic functioning in MetS patients [15]. More specifically, decreased vagal activity was found in individuals with obesity [16], dysglycaemia [17], hypertension [18, 19] and hyperlipidaemia [20], suggesting perturbation of cholinergic pathways in MetS. One possible cause of impaired vagal activity is the increase in butyrylcholinesterase (BChE)‐mediated hydrolysis of acetylcholine (ACh) observed in early T2DM patients, followed by BChE decreases in established patients [21].…”