title: Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans.
abstract: 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 kg m⁻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 α2-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.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523-1582, USA.
authors.forename: Garrett L
authors.initials: GL
authors.lastname: Peltonen
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Scalzo
authors.forename: Melani M
authors.initials: MM
authors.lastname: Schweder
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Larson
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Luckasen
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Hamilton
authors.forename: Thies
authors.initials: T
authors.lastname: Schroeder
authors.forename: Christopher
authors.initials: C
authors.lastname: Bell
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003000:Clonidine / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013565:Sympatholytics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D013565:Sympatholytics; D003000:Clonidine