The Mechanism Of Oxidative Stess And Mapks Signal Transduction Pathway Induce Insulin Resistance In Rats With Type 2 Diabetes

Objective The objective of the present study was to test whether oxidative stress and MAPKs family contribute to the pathogenesis of insulin resistance in rat with type 2 diabetes.Methods Male Sprague-Dawley rats were divided into two groups and fed with commercially available normal diet or in-house prepared high-fat diet (T2DM)(composed by 250ml pork fat and 5g Cholesterol) for a period of 3 months. After 3 months of dietary manipulation,a subset of the rats from T2DM groups was injected intraperitoneally with low dose of streptozotocin(STZ,20 mg/kg) two times and fed to high-fat diet for 2 months again,then experimental rats were examined GSP,triglycerides(TG),total cholesterol(TCHOL),C reactive protein(CRP), C-peptide(C-P) levels,insulin(INS),GLU and Insulin Resistance Index(IR).The activity of the Nitric oxide synthase(NOS),inducible nitric oxide synthase(INOS), Nitric Oxide(NO),malondialdehyde(MDA),glutathione(GSH),Glutathionereductase (GR),anti-oxidative capabilities(T-AOC),total superoxide dismutase(T-SOD) activities were examined by colorimetric method.The P38,JNK and ERK were examined by western blotting.Results The T2DM rats exhibited significant increase in body weight,TG,TCHOL,CRP,C-P levels,INS,and Insulin Resistance Index(IR) in glucose on oral insulin glucose tolerance test(OGTT) as compared to ND-fed control rats.Besides,the T2DM rats showed significant increasing FGLU, CRP,INS,TG,TCHOL,IR and GLU,INS,C-P in OGTT-2 hour as compared to T2DM and ND rat.At the same time,Chronic systemic exposure of HFD+STZ to rats induced insulin resistance and increased in liver oxidative stress,including an increase in MDA,NOS,INOS and GR(P＜0.05),while a decrease in NO andGSH(P＜0.05). The significant deviation was not detected in T-AOC,T-SOD.In addition,Chronic systemic exposure of HFD+STZ to rats has an increase in P-P38 and P-JNK(P＜0.05), while a decrease in P-ERKP42/P44(P＜0.05).Hyperinsulinemia together with increasing IR suggested that the feeding of HFD+STZ can induce the insulin resistance in rats.Conclusion Oxidative stress may contribute to the pathogenesis of insulin resistance by manipulating MAPKs family in rat with type 2 diabetes.