The roles of sex and
sex-hormones on the metabolic consequences of intermittent
hypoxia (IH, a reliable model of
sleep apnea) are unknown. We used intact male or female mice and ovariectomized (OVX) females treated with vehicle (Veh) or
estradiol (E2) and exposed to normoxia (Nx) or IH (6% O2, 10 cycles/h, 12 h/day, 2 wk). Mice were then fasted for 6 h, and we measured fasting
glucose and
insulin levels and performed
insulin or
glucose tolerance tests (ITT or GTT). We also assessed liver concentrations of
glycogen,
triglycerides (TGs), and expression levels of genes involved in aerobic or anaerobic metabolism. In males, IH lowered fasting levels of
glucose and
insulin, slightly improved
glucose tolerance, but altered
glucose tolerance in females. In OVX-Veh females, IH reduced fasting
glucose and
insulin levels and strongly
impaired glucose tolerance. E2 supplementation reversed these effects and improved homeostasis model assessment of β-cell function (HOMA-β), a marker of pancreatic
glucose-induced
insulin released. IH decreased liver TG concentration in males and slightly increased
glycogen in OVX-Veh females. Liver expression of glycolytic (Ldha) and mitochondrial (
citrate synthase, Pdha1) genes was reduced by IH in males and in OVX-Veh females, but not in intact or OVX-E2 females. We conclude that 1) IH reduced fasting levels of glycemia in males and in ovariectomized females. 2) IH improves
glucose tolerance only in males. 3) In females IH decreased
glucose tolerance, this effect was amplified by
ovariectomy, and reversed by E2 supplementation. 4) During IH exposures, E2 supplementation appears to improve pancreatic β cells functions.NEW & NOTEWORTHY We assessed fasting
glycemic control, and tolerance to
insulin and
glucose in male and female mice exposed to intermittent
hypoxia. IH improves
glucose tolerance in males but had opposite effects in females. This response was amplified following
ovariectomy in females and prevented by
estradiol supplementation. Metabolic consequences of IH differ between males and females and are regulated by
estradiol in female mice.