Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans

• Published in: The Journal of physiology 2012-06, Vol.590 (11), p.2801-2809
• Main Authors: Peltonen, Garrett L., Scalzo, Rebecca L., Schweder, Melani M., Larson, Dennis G., Luckasen, Gary J., Irwin, David, Hamilton, Karyn L., Schroeder, Thies, Bell, Christopher
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - analysis; Clonidine - pharmacology; Humans; Hypoxia - physiopathology; Insulin Resistance - physiology; Integrative; Male; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology; Sympatholytics - pharmacology; Young Adult
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2011.227090

Key points •  In low‐oxygen environments, such as high‐altitude, control of blood sugar is disrupted. Further, the activity of the sympathetic nervous system is known to increase when the availability of oxygen is decreased. •  We have investigated the possibility that the increase in sympathetic activity is partially responsible for the disruption in blood sugar control. •  Using gasbags filled with low‐oxygen gas, together with a commonly used blood pressure medication (clonidine) that inhibits the sympathetic nervous system, we have shown that breathing low oxygen disrupts blood sugar control, and that this disruption is prevented when the nervous system is inhibited. •  This finding has important implications for people travelling to high altitudes, and for people who suffer from conditions characterized by low oxygen, such as sleep apnoea and lung diseases.   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 (= 0.21), hypoxia (= 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 in