Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans

Acute exposure to hypoxia decreases insulin sensitivity in healthy adult humans; the mechanism is unclear, but increased activation of the sympathetic nervous system may be involved. We have investigated the hypothesis that short-term sympathetic inhibition attenuates hypoxia induced insulin resistance. Insulin sensitivity (via the hyperinsulinaemic euglycaemic clamp) was determined in 10 healthy men (age 23+/- 1 years, body mass index 24.2+/- 0.8 kgm-2 (means+/- SEM)), in a random order, during normoxia (FIO2 = 0.21), hypoxia (FIO2 = 0.11), normoxia and sympathetic inhibition (via 48 h transdermal administration of the centrally acting a2-adrenergic receptor agonist, clonidine), and hypoxia and sympathetic inhibition. Oxyhaemoglobin saturation (pulse oximetry) was decreased (P< 0.001) with hypoxia (63+/- 2%) compared with normoxia (96+/- 0%), and was unaffected by sympathetic inhibition (P> 0.25). The area under the noradrenaline curve (relative to the normoxia response) was increased with hypoxia (137+/- 13%; P = 0.02); clonidine prevented the hypoxia induced increase (94+/- 14%; P = 0.43). The glucose infusion rate (adjusted for fat free mass and circulating insulin concentration) required to maintain blood glucose concentration at 5 mmol l-1 during administration of insulin was decreased in hypoxia compared with normoxia (225+/- 23 vs. 128+/- 30 nmol (kg fat free mass)-1 pmol l-1 min-1; P = 0.03), and unchanged during normoxia and sympathetic inhibition (219+/- 19; P = 0.86) and hypoxia and sympathetic inhibition (169+/- 23; P = 0.23). We conclude that short-term sympathetic inhibition attenuates hypoxia induced insulin resistance.