Background: In chronic
hypoxia (CH) and short-term chronic intermittent
hypoxia (CIH) exposure, glycemia and
insulin levels decrease and
insulin sensitivity increases, which can be explained by changes in
glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of
hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX) and compared the findings. Methods: Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr) group (n = 10), a CIH group (2 days
hypoxia/2 days NX; n = 10) and a CH group (n = 10). Rats were exposed to
hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m). Feeding (10 g daily) and fasting times were accurately controlled. Measurements included food intake (every 4 days), weight, hematocrit,
hemoglobin, glycemia, serum
insulin (by ELISA), and
insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30. Results: (1)
Weight loss and increases in hematocrit and
hemoglobin were found in both hypoxic groups (p < 0.05). (2) A moderate decrease in glycemia and plasma
insulin was found. (3)
Insulin sensitivity was greater in the CIH group (p < 0.05). (4) There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5) The level of activated AMPK was increased only in the CIH group (p < 0.05). (6) Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group (p < 0.05). Conclusion: In lean rats experiencing long-term CIH, glycemia and
insulin levels decrease and
insulin sensitivity increases. Interestingly, there is no increase of GLUT1 or GLUT4 levels or in Akt activation. Therefore, cellular regulation of
glucose seems to primarily involve GLUT4 translocation to the cell membrane in response to
hypoxia-mediated AMPK activation.