The Effects Of Noise Exposure On Insulin Sensitivity And Related Mechanism In Mice

Noise pollution is one of the serious environmental problems in modern society.In recent years,several large sample population-based studies respectively indicate that noise exposure has significantly positive correlation with a higher risk of diabetes and many diseases of the cardiovascular system,but its associated mechanism is unclear.Our previous work showed that animals appeared normal blood glucose-hyperinsulinemia,prompting that noise exposure may cause insulin resistance(IR).IR refers to the sensitivity and responsiveness of insulin target tissues to endogenous or exogenous insulin decreased,leading to the normal dose of insulin cannot achieve a normal biological effect.IR is not only the characteristics of type 2 diabetes(T2DM),but also the common pathological basis of T2DM and a variety of cardiovascular diseases(common soil theory).Although it is known that IR is the interaction result of genetic factors and environmental factors,but the influence of noise exposure on insulin sensitivity has not yet seen in the research report.Our research will experiment on the ICR mice,and focus on the effect of noise exposure on insulin sensitivity and the related mechanism.This study has a vital practical significance on preventing IR,and controlling the development of T2DM and cardiovascular diseases.Healthy male ICR mice with normal hearing was taken as the research object.The mice in research were grouped randomly and then exposed in noise(95dB SPL,broad white noise,4h/day)for one day(N1D group),for 10 consecutive days(N10D group),and for 20 consecutive days(N20D group).The same batch which was not given noise is taken as control group of the same age.According to the end times[after noise exposure for one day,one week and one month(1DPN,1WPN,1MPN)],each group is divided into three sub groups for terminal testing or sampling.The effects of noise exposure on insulin sensitivity of mice at the individual level was measured by metabolic efficiency and insulin tolerance test.The effects of noise exposure on skeletal muscle insulin sensitivity and related mechanism was measured by immunofluorescence and Western blot experiments at the cellular level and insulin signaling pathway level.In order to study the molecular mechanism of insulin resistance in skeletal muscle caused by noise exposure at the individual level,the stress and inflammatory cytokines in their serum and tissue were measured.The experimental results show that:(1)After noise exposure,there was no significant increase in the auditory threshold of the animals in noise group,showing that the noise exposure did not have a significant impact on animal hearing.(2)After the noise exposure,the weight gain rate of chronic noise group was significantly higher than that of the control group.And metabolic efficiency is significantly lower than control,suggesting that the animals exposed to chronic noise exposure appeared abnormal metabolism.(3)According to insulin tolerance test,the extent of transient decreased insulin sensitivity(IR)caused by noise exposure has a significant positive correlation with noise exposure dose(days).(4)Results of Immunofluorescence of the skeletal muscle showed that parallel to the insulin tolerance test,the key molecule,glucose transporter 4(GLUT4)in insulin signaling pathway of the cell membrane translocation in noise group animal appeared transient decrease,and the decrease is positively related to the dose of noise exposure.(5)Westem blot results showed that and expression of GLUT4 and protein kinase B(protein kinase B,Akt)phosphorylation appeared transient decrease,but Jun N-terminal kinase(Jun N-terminal kinase,JNK)phosphorylation and insulin receptor substrate(insulin receptor substrate,IRS)of the serine phosphorylation level of noise group animals increased,indicating that the insulin resistance in noise group animal 's skeletal muscle was associated with intracellular JNK excessive activation and its related IRS-Akt insulin signaling pathway.(6)The results of serum ELISA showed that parallel to the IR at overall level and the tissue level,serum corticosterone(corticosterone,CORT)hormone appeared transient increase in noise group,the results not only show that although the noise exposure have not cause hearing loss,it has caused stress to the mice,but also showed that animals in chronic noise exposure group had persistent higher stress levels.Inflammatory factors significantly increased in animals with chronic noise exposure.All these results indicate that,the stress response and inflammatory reaction may be the mediator of IR caused by noise exposure(especially the chronic noise exposure).(7)Skeletal muscle tissue homogenate of oxidative stress test results showed that the noise group animals appeared a significant increase in the level of oxidative stress.Lipid peroxidation products MDA increased in 1 WPN,and the increase of chronic noise group was much higher than that of the acute noise group,this is maybe the result of disorder that causes the accumulation of lipid peroxidation products in cells.This part suggests that the persistent increase in the level of tissue oxidative stress may lead to more serious and lasting IR in chronic noise group.IR is the result of the interaction between environmental factors and genetic background,and its promoting factors and mechanisms have been the focus in the research.Our study first demonstrated that IR can be caused by noise exposure with animal experiments from the whole level and the level of tissue and cells.Although this study can't reveal the complete mechanism of IR induced by noise exposure,according to our results and literature,we can put forward the following hypothesis:noise exposure in this research did not cause significant hearing loss,but has caused stress to the mice;Increase of CORT in blood after acute noise exposure caused transient increase of oxidative stress in tissue.Kinase JNK in stress response of the skeletal muscle cell is activated,causing the IRS serine phosphorylation and inhibiting Akt activation and GLUT4 dislocation on cell membrane,thus reducing the glucose uptake by skeletal muscle under insulin stimulates,causing transient IR;Chronic noise exposure is not only make the mice in a state of chronic persistent stress,but also caused stronger inflammatory reaction,making the oxidative stress in skeletal muscle tissue more serious and lasting longer,leading to more severe and lasting IR.With the rapid development of modem society,the widespread threat to public health caused by noise pollution has become more and more serious.However,due to its broad existence and the invisible damage of noise exposure to the body,it is more properly become a "stealth killer" to human health.The research results can not only enhance the awareness of the whole society to noise pollution,which has guiding significance for preventing IR and its related diseases,but also provide credible laboratory basis for optional intervention target of related diseases.