Abstract
Obstructive sleep apnea syndrome (OSA) is described as an independent risk factor for the onset and progression of type 2 diabetes (T2DM), as well as for insulin resistance (IR). The mechanisms underlying these processes remain unclear. One of the proposed molecular mechanism is based on the oxygen-sensitive α-subunit of hypoxia-inducible factor 1 (HIF-1α)—a key regulator of oxygen metabolism. The concept that stabilization of HIF-1α may influence T2DM and IR is supported by cell and animal models. Cell culture studies revealed that both glucose uptake and glycolysis are regulated by HIF-1α. Furthermore, animal models indicated that increased fasting glucose may be caused by a single night with intermittent hypoxia. Moreover, in these models, hypoxia time was correlated with IR. Mice models revealed that inhibition of HIF-1α protein may downregulate fasting blood glucose and plasma insulin level. Administration of superoxide dismutase mimetic resulted in inhibition of HIF-1α protein, catecholamines, and chronic intermittent hypoxia-induced hypertension in a mice model. The hypothesis that hypoxia is an independent risk factor for IR is strengthened by experimentally confirmed improvement of insulin sensitivity among OSA patients treated with the continuous positive airway pressure. Furthermore, recent studies suggest that HIF-1α protein concentration is increased in individuals with OSA. In this literature review, we summarize the current knowledge about HIF-1α in OSA in relation to the possible pathways in which they contribute to metabolic disorders.
Highlights
Obstructive sleep apnea (OSA) constitutes a rapidly growing health problem in the modern world (Gabryelska and Białasiewicz, 2020)
The same study provides the data suggesting that hypoxia can lead to the downregulation of selected genes, which play important roles in β-cell function: Foxa2, Mafa, Ins1, Neurod1, Pdx1, Wfs1, Slc2a2, Kcnj11, and Ndufa5 in both mouse islets and MIN6 cells; majority of the hypoxia-induced gene downregulations in cells were not related to hypoxia-inducible factors (HIF)-1α suppression, suggesting a α-subunit of hypoxia-inducible factor 1 (HIF-1α)-autonomous mechanism (Sato et al, 2014)
Investigation of the effect of certain glucose concentrations on HIF-1α expression in human dermal fibroblasts (HDF) at normoxia and hypoxia showed that HIF-1α expression depends on glucose concentration only in hypoxia
Summary
Obstructive sleep apnea (OSA) constitutes a rapidly growing health problem in the modern world (Gabryelska and Białasiewicz, 2020). Recent data suggest that the moderate and severe form of this disorder affect between 6 and 17% adults in the general population (Senaratna et al, 2017), while some research suggest that its prevalence is up to 23% among women and 49% among men (Heinzer et al, 2016) This trend may be an effect of increasing frequency of overweight/obesity, which is one of the strongest modifiable OSA risk factors. Bulcun et al (2012) observed that progression from snoring and/or mild OSA to severe OSA led to increased frequency of abnormal glucose metabolism They suggested regular examination of possible glucose metabolism derangements among OSA patients, especially those with severe OSA (Bulcun et al, 2012). A meta-analysis revealed that OSA predicted risk of metabolic syndrome, independently of obesity (Mesarwi et al, 2015; Qian et al, 2016); Coughlin et al (2004) observed that metabolic syndrome was over nine times more likely to be present among OSA patients
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