Intermittent
hypoxia (IH) is a frequent occurrence in sleep and respiratory disorders. Both human and murine studies show that IH may be implicated in metabolic dysfunction. Although the effects of nocturnal low-frequency intermittent
hypoxia (IH(L)) have not been extensively examined, it would appear that IH(L) and high-frequency intermittent
hypoxia (IH(H)) may elicit distinct metabolic adaptations. To this effect, C57BL/6J mice were randomly assigned to IH(H) (cycles of 90 s 6.4% O(2) and 90 s 21% O(2) during daylight), IH(L) (8% O(2) during daylight hours), or control (CTL) for 5 wk. At the end of exposures, some of the mice were subjected to a
glucose tolerance test (GTT; after
intraperitoneal injection of 2 mg
glucose/g body wt), and others were subjected to an
insulin tolerance test (ITT; 0.25 units
Humulin/kg body wt), with plasma
leptin and
insulin levels being measured in fasting conditions. Skeletal muscles were harvested for GLUT4 and proliferator-activated receptor gamma coactivator 1-α (PGC1-α) expression. Both IH(H) and IH(L) displayed reduced
body weight increases compared with CTL. CTL mice had higher basal glycemic levels, but GTT kinetics revealed marked differences between IH(L) and IH(H), with IH(L) manifesting the lowest
insulin sensitivity compared with either IH(H) or CTL, and such findings were further confirmed by ITT. No differences emerged in PGC1-α expression across the three experimental groups. However, while cytosolic
GLUT4 protein expression remained similar in IH(L), IH(H), and CTL, significant decreases in GLUT4 membrane fraction occurred in
hypoxia and were most pronounced in IH(L)-exposed mice. Thus IH(H) and IH(L) elicit differential
glucose homeostatic responses despite similar cumulative hypoxic profiles.