Effects of AMPK activation on insulin resistance and inflammatory factors in rats with chronic intermittent hypoxia / 重庆医学

ABSTRACT

Objective To investigate the effect and mechanism of adenosine monophosphate activated protein kinase(AMPK) activation on insulin resistance and inflammatory factors in rats with chronic intermittent hypoxia.Methods The chronic intermittent hypoxia rat model was established to simulate the obstructive sleep apnea syndrome (OSAS),and the 36 male SD rats were divided into the normal oxygen control group,2-week intermittent hypoxia group and 8-week intermittent hypoxia group.The levels of rat inflammatory medium,serum lipid,adiponectin,leptin and insulin resistance in different hypoxia degrees of rats by the action of AMPK agonist and AMPK inhibitor were observed,and the levels of AMPK and GLUT4 in rat adipose tissue were monitored and statistically analyzed.Results The levels of total cholesterol,triglyceride,TNF-α,IL-6,IL-2,NF-κB and HIF-1 in the intermittent hypoxia rats were significantly higher than those in the control group(P＜0.05);while the levels of adiponectin,leptin and insulin resistance index were significantly lower than those in the control group(P＜0.05).The release of inflammatory factors in rats after using AMPK activator was decreased,the contents of adiponectin and leptin were increased,blood lipid and insulin resistance were improved compared with before,and the expression level of GLUT4 was increased.But after treatment by using AMPK inhibitor,the levels of inflammatory factors,adiponectin and leptin were increased,insulin resistance was more severe,and the expression level of GLUT4 protein was also further decreased.Conclusion AMPK can reduce the release of inflammatory mediators,promotes the release of adiponectin and leptin,increases the level of GLUT4,improves insulin resistance,thus regulates the energy metabolism and inflammatory mediators,which provides a new idea and target for clinical treatment of OSAS related diseases.