| BackgroundAccording to the sixth edition of IDF DIABETES ATLAS,there are the majority of the 382 million people with diabetes worldwide in 2013.A further 316 million adults are estimated to have impaired glucose tolerance.Diabetes caused 5.1 million deaths in 2013.Every six seconds a person dies from diabetes.The burden of diabetes is enormous,provoking 5.1 million deaths and taking up some USD 548 billion dollars in health spending in 2013.By 2035,we also estimate there are 592 million adults with diabetes worldwide and and USD 627 billion in healthcare spending.According to the seventh edition of IDF DIABETES ATLAS,there are the majority of the 415 million people with diabetes worldwide in 2015,there is an increase of 8.64% than 2013,a further 318 million adults are estimated to have impaired glucose tolerance,there is an increase of 0.63% than 2013,Diabetes caused 5.0 million deaths in 2015.Every six seconds a person dies from diabetes.In human as well as financial terms,the burden of diabetes is enormous,provoking 5.0 million deaths and taking up some USD 673 billion dollars in health spending in 2015.By 2040,we also estimate there are 642 million adults with diabetes worldwide and and USD 880.8 billion in healthcare spending.The prevalence of diabetes is increasing in recent years and diabetes has became one of the major public health issues.Genetic factors and environmental factors together lead to diabetes.Epidemiological and experimental data show that organophosphorus pesticides exposure can increase the morbitity and mortality.Omethoate is one of the organophosphorus pesticides with high toxicity,fast action and low Residue.The pathological mechanisms of diabetes include decreased β cell mass and insulin resistance.Disfunction of insulin signal is the cause of major pathological mechanism of insulin resistance.The liver is the largest gland,the most important digestive organ,metabolic organ and defense organ,but also the body’s metabolic hub.Omethoate was administered to ICR male mice for 8 weeks,the components of in Insulin signal pathway were determined to investigate the effects of omethoate on Insulin signal pathway in the liver of mice exposed to omethoate.ObjectiveTo explore the effects of omethoate on the levels of glucose,insulin signal pathway and related mechanisms of in the liver of mice.Methods1.Experimental grouping and processing: Fifty ICR male mice were randomly divided into five groups: Control group,Vehicle group,L-dose group,M-dose group and high-dose group.The control mice were given saline,the Vehicle mice were given oily corn oil,the low dose mice were intragastrically given 0.5 mg / kg bw dose of omethoate,the middle dose mice were given gavage at 1 mg / kg bw dose of omethoate,High-dose mice were given at 2 mg / kg bw dose of omethoate.After administered 8 weeks,all mice were killed and samples were collected.2.Blood glucose level: The levels of glucose were examined by Blood glucose meter.3.Blood lipid level: Kits were used to detect serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)in mice.4.Insulin signal pathway: The protein of P38-MAPK,IRS-1,NF-κB,PPAR-γ,GLUT-4,PI3 K in liver of mice were quantified with western blot.5.Liver apoptosis: The protein of Bax、Bcl-2 and FADD in liver of mice were quantified with western blot.Results1.Body weight of mice: The body weight of mice was no significant difference among five groups.2.The levels of glucose: The levels of glucose was no significant difference among five groups.3.Organ coefficient: The organ coefficient of liver,heart,spleen,lung and kidney were no significant difference among five groups.4.Blood lipid level: The level of serum TC of mice from Control and L-dose groups was significantly lower than that mice from M-dose group(P<0.05);the level of serum TC of mice from H-dose group was significantly higher than other groups(P<0.05).The level of serum TG of mice from H-dose group was significantly higher than other groups(P<0.05).The level of serum HDL-C of mice from L-dose and M-dose groups was respectively lower than that mice from Control and Vehicle groups(P<0.05);.the level of serum HDL-C of mice from Control,Vehicle and L-dose groups was significantly higher than that mice from H-dose group(P<0.05).The level of serum LDL-C of mice from Control,Vehicle and L-dose groups was significantly lower than that mice from M-dose and H-dose groups(P<0.05).5.Insulin signal pathway : The expression level of IRS-1 and PI3 K protein in the liver of mice from Control group,Vehicle group and L-dose group was significantly higher than that mice from M-dose group and H-dose group(P<0.05).The expression level of Akt protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly higher than that mice from H-dose group(P<0.05).The expression level of GLUT4 protein in the liver of mice from Control group,Vehicle group and L-dose group was significantly higher than that mice from H-dose group(P<0.05).The expression level of P38-MAPK protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly lower than that mice from H-dose group(P<0.05).6.Liver apoptosis: The expression level of Caspase8,FADD and Bax protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly lower than that mice from H-dose group(P<0.05).The expression level of Bcl2 protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly higher than that mice from H-dose(P<0.05).The relative value of Bax / Bcl2 in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly lower than that mice from H-dose group(P<0.05).7.The expression level of PPAR-γ protein: The expression level of PPAR-γ protein in the liver of mice from Control group,Vehicle group and L-dose group was significantly higher than that mice from M-dose group and H-dose group(P<0.05).8.The expression level of PGC-1α protein: The expression level of PGC-1α protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly lower than that mice from H-dose group(P<0.05).9.The expression level of NF-κB protein: The expression level of NF-κB protein in the liver of mice from Control group,Vehicle group,L-dose group and M-dose group was significantly lower than that mice from H-dose group(P<0.05).Conclusion1.Omethoate exposure can cause blood lipid disorders;2.Omethoate exposure could affect the expression of key proteins in the hepatic insulin signal transduction pathway;3.Omethoate exposure to mice can increase the cell apoptosis proteins of Bax and FADD,Omethoate exposure also can decrease the cell apoptosis protein of Bcl-2;4.Omethoate exposure to mice can increase the expression of PGC-1α protein,and decrease the expression of PPAR-γ protein. |
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