D occulted type two diabetes inside the non-overweight group. Moreover, the impact
D occulted type two diabetes inside the non-overweight group. Moreover, the impact of CPAP therapy could be diverse in between obese and non-obese subjects. Harsch et al. (2004b) showed that the improvement in insulin sensitivity was much smaller in obese subjects than in non-obese subjects, suggesting that in obese individual’s insulin sensitivity is mostly determined by obesity and, to a smaller extent, by sleep apnea. Obesity is known to be strongly related with metabolic dysfunction, and that contributes to insulin resistance and glucose intolerance (Landsberg, 1996, 2001), nonetheless metabolic dysfunction could be present in lean OSA subjects (Pamidi et al., 2012). In CIH rodent models metabolic dysfunction is present without the need of the obesity component (Carreras et al., 2012; Fenik et al., 2012; Wang et al., 2013; Shin et al., 2014), as it was described that animals submitted to CIH achieve much less weight (Carreras et al., 2012) or the comparable weight (Olea et al., 2014) in comparison with controls. Also, the amounts of perirenal and CXCR4 supplier epididymal fat located in CIH animals was comparable to those identified in controls (Olea et al., 2014). Taken collectively these outcomes show that in OSA, obesity just isn’t the only aspect that contributes to metabolic dysfunction. The involvement of CB has been recently proposed as certainly one of the links involving CIH and sympathetic overactivity and metabolic dysfunction, considering that CB denervation prevents CIHinduced fasting hyperglycemia, although CB denervation was incapable of avoid insulin resistance (Shin et al., 2014), suggesting that other mechanisms can account for the CIH inducedinsulin resistance. Actually, little is identified concerning the molecular mechanisms behind this partnership, using the reduction of Glut4 metabolic fraction in skeletal muscle in CIH animals getting the only mechanism described (Carreras et al., 2012). Thus, detailed studies around the molecular mechanisms of insulin action in insulin-sensitive tissues will contribute enormously to better have an understanding of the paradigm of CIH-induced insulin resistance, and so the connection between OSA and metabolic dysfunction.FUTURE PERSPECTIVESIn the last couple of years, many reports of non-classical roles of the CB on glucose homeostasis and metabolic regulation havefrontiersin.orgOctober 2014 | Volume five | Article 418 |Conde et al.Carotid body and metabolic dysfunctionbeen published, contributing to launch the CB as a putative therapeutic target for the therapy of endocrine ailments. Our group has been actively involved inside the method and not too long ago we described that chronic CB overstimulation is implicated in the etiology of diet-induced insulin resistance (Ribeiro et al., 2013). We have also described that surgical resection of the CSN prevents the improvement of dysmetabolic alterations induced by hypercaloric therapies in rats (Ribeiro et al., 2013), an observation that contributed to strengthen that CB blockademodulation represents a novel and unexploited therapeutic strategy. Apart from the surgical resection in the CB, its overactivation may also be prevented pharmacologically with an old, well-studied and quite safe drug: caffeine. Sustained caffeine administration prevents the development of Caspase 11 Storage & Stability hypertension, impaired glucose tolerance and insulin resistance in prediabetes animal models (Conde et al., 2012b; Panchal et al., 2012). The protective effect of chronic caffeine administration was accompanied by prevention of weight achieve and decreased visceral fat in obese animals;.