Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) is a feature of obstructive sleep apnea (OSA). Whereas clinical stud-ies have demonstrated the association between OSA and insulin resistance, the molecular mechanismsbehind it are still unknown. Herein we investigated the effect of mild CIH on insulin sensitivity and weevaluated the changes in insulin and HIF signaling pathways that occur in CIH-induced insulin resistance.We showed that mild CIH obtained by 5/6 hypoxic (5%O2) cycles/h, 10.5 h/day during 28 and 35 daysincreased arterial blood pressure. Insulin resistance and insulinemia increased with CIH duration, beingsignificantly different after 35 days of CIH. Thirty-five days of CIH decreased insulin receptor expressionand phosphorylation in skeletal muscle and adipose tissue, but not in the liver. Conversely, Glut2 expres-sion increased in the liver of CIH-animals. Thirty-five days of CIH up-regulated HIF-1 in the liver anddown-regulated HIF-1 and HIF-2 in skeletal muscle.We concluded that the effect of CIH on insulin sensitivity and signaling is time-dependent and isassociated with changes in HIF signaling in insulin-sensitive tissues.

Keywords

Chronic intermittent hypoxia Insulin resistance Obstructive sleep apnea Insulin signaling and HIF signalinga

URI

http://hdl.handle.net/10400.8/13071

Citation

J.F. Sacramento, M.J. Ribeiro, T. Rodrigues, M.P. Guarino, L.N. Diogo, R. Seiça, E.C. Monteiro, P. Matafome, S.V. Conde, Insulin resistance is associated with tissue-specific regulation of HIF-1α and HIF-2α during mild chronic intermittent hypoxia, Respiratory Physiology & Neurobiology, Volume 228, 2016, Pages 30-38, ISSN 1569-9048, https://doi.org/10.1016/j.resp.2016.03.007.