| Diabetes has become one of the most important chronic non-communicable diseases that threaten human health in the world,and it is showing a worldwide trend.The growing prevalence of diabetes imposes a heavy economic burden on society,so it is of great importance to actively control and treat T2 DM.Therefore,in this experiment,the experimental diabetic KKAy mice were given the fish oil rich in Omega-3 PUFA every day to record the routine data of the mice during the experimental period.After the experimental period,the serum and tissue of the diabetic mice were tested,and the mechanism of the action of fish oil to improve the insulin resistance was further studied.It has important theoretical value and application prospect for promoting the development of nutritional therapy and prevention of type 2 diabetes in Chinese patients with type 2 diabetes.Objective:To investigate the effects of fish oil on glucose and lipid metabolism and phosphatidylinositol 3-kinase(PI3K)/protein Kinase B(Akt)signaling pathway in diabetic KKAy mice and provide scientific basis for the mechanism of fish oil on glucose and lipid metabolism and insulin resistance..Methods:Eight-week-old specified pathogens free male KKAy mice Forty KKAy mice was fed high-fat diet after a week of acclimization period.After 4 weeks,the mice with the fasting blood glucose over 13.9mmol/L were considered as qualified model mice.Forty KKAy diabetic mice were randomly assigned into four groups: diabetic model group,low-dose fish oil group,medium-dose fish oil group and high-dose fish oil group.Model control(MC)group was fed high-fat diet accompanied by daily gavage with 5‰ carboxy methyl cellulose sodium.Fish oil(FO)group was fed high-fat diet accompanied by daily gavage with different dose of fish oil(25.8%EPA and 36.4%DHA per 1g).Low dose FO group,medium dose FO group,high dose FO group received intragastrically FO at a dose of 0.67 g/kg,1.33 g/kg,2.0 g/kg,respectively.Ten eight-week-old specified pathogens free male C57BL/6 mice served as a non-diabetic control group was fed normal diet accompanied by daily gavage with 5‰ carboxy methyl cellulose sodium.The animals were fasted for 12-14 hours and blood and tissue samples were collected after 12 weeks of treatment.Serum glucose,triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C)were determined by automatic biochemical analyzer(Beckman,DxC800).Serum insulin,adiponectin,leptin and interleukine-6(IL-6),Tumor necrosis factor-alpha(TNF-?),C-Reactive protein(CRP)were measured using Elisa kits.The liver tissue was stained with eosin-hematoxylin for pathological examination.The expression of IRS-1,PI3 K,Akt,GLUT-4 and GSK3? in Liver and skeletal muscle tissue were examined by RT-PCR and western-blot.Results:Compared with the normal control group,the blood glucose,HOMA-IR,TG,TC,HDL-C,LDL-C and CRP levels in the model control group significantly increased(P<0.05).Compared with the model group,FBG was reduced significantly in low-dose fish oil group(P<0.01),FINS was increased in low and medium dose of fish oil group(P<0.05),adiponectin level was significantly increased in each fish oil group(P<0.05).After fish oil intervention,HOMA-IR in the low-dose fish oil group showed a significant downward trend.TG,TC,HDL-C,LDL-C in fish each fish oil group had no differences from model group.Under one-hundred-fold light microscopy,the hepatic steatosis at the low,medium,and high doses of fish oil group showed a certain degree of improvement.In addition,RT-PCR results showed that compared with the model group,there was no significant differences in the gene expression of PI3 K,Akt,and GSK3? in the liver of each fish oil group.Compared with the model group,low,medium and high dose group of fish oil can up-regulate gene expression of IRS-1,PI3 K,Akt,GLUT-4,low dose group of fish oil had more significant effect on the gene expression of Akt and the GLUT-4 in the skeletal muscle.Western Blot showed that compared with the normal control group,the expression of GSK3? protein in the liver of model group and fish oil group was significantly increased(P<0.05).Compared with the model group,the expression of IRS-1,PI3 K,p-Akt,and GLUT-4 protein increased in the skeletal muscle of each fish oil group,the low-dose fish oil group had a more significant effect on the regulation of GLUT-4 protein.Conclusion:Fish oil supplement had no statistically significant effects on lipid metabolism.Low-dose fish oil group can significantly reduce the blood glucose level of KKAy diabetic mice,and it is more effective for the improvement of insulin resistance and glucose metabolism.The low dose group of fish oil has more significant regulation effect on the expression of individual genes and proteins.Low dose group of fish oil may improve glucose metabolism and IR by regulating adiponectin levels and the PI3K/Akt signaling pathway. |
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