| Objective:By investigating the changes in body weight,blood glucose,insulin,lipids,TNF-?,and IL-6 by high-fat diet,determine whether,whether type 2 diabetes(T2DM)insulin resistance model mice were successfully established and whether the intervention of resolving D1(RvD1)can improve insulin resistance(IR)in type 2 diabetes mellitus(T2DM)mice.By observing the levels of IRS-1,P-IRS-1(Tyr896),P-IRS-1(Ser307),GLUT4,and NF-?B proteins in mouse adipose tissue,reveal the specific mechanism of RvD1 and provide a theoretical basis for its clinical application.Methods:Thirty-five male C57BL/6 mice were used as experimental subjects.After one week of feeding,they were randomly divided into blank control group(NC group)and high-fat diet(HFD)group.After 8 weeks of feeding on an ordinary diet and a high-fat diet,After injection of streptozotocin(STZ,100mg/kg),after 3 days blood glucose ?16.7 mmol/L was measured in T2 DM model mice,with abandoning the unsuccesful mice,the remaining mice model were randomly divided into type 2 diabetes group(T2DM group)and type 2diabetes+RvD1 intervention group(T2DM+RvD1 group).Two groups of mice were intraperitoneally injected with PBS solution 0.2ml/day and Rv D1100ng/day for 21 consecutive days.Animals were killed by decapitation,and body weight and blood glucose levels were monitored regularly and detected the mice of blood lipids in,Serum insulin levels and TNF-?,IL-6 levels.To determine whether RvD1 can improve adipose tissue IR in T2 DM mice and to understand its possible mechanisms,the fresh mouse adipose tissue were detected to analysis of IRS-1,P-IRS-1(Tyr896),P-IRS-1(Ser307),GLUT4,NF-?B protein by Western blot.Result:1.Changes in body weight in miceBefore modeling,weight of mice in NC group increased slowly,and body weight in mice in the HFD group increased rapidly.After modeling,Compared with NC group,the weight of mice in T2 DM group and T2DM+RvD1 group was significantly increased,and the difference was statistically significant(P<0.05).Compared with the T2 DM group,after 3 weeks of intervention with RvD1,the body weight of mice in the T2DM+RvD1 group was significantly reduced(P<0.05).2.Change of blood glucose,insulin and insulin resistance index(HOMA-IR)levels in miceDuring the experimental period,the blood glucose level of mice in NC group was not significantly changed.Prior to model establishment,blood glucose levels in HFD mice gradually increased.After modeling,Compared with NC group,the levels of blood glucose,insulin and insulin resistance in T2 DM group and T2DM+RvD1 group were significantly higher(P<0.05).After 3 weeks of RvD1 intervention,Compared with the T2 DM group,the blood glucose levels of mice in T2DM+RvD1 group were decreased(P<0.05).The levels of insulin and insulin resistance index in mice of T2DM+RvD1group were reduced,and the difference was statistically significant(P<0.05).3.Changes in blood lipid levels in miceCompared with the NC group,the blood cholesterol(CHOL)and triglyceride(TG)levels in the T2 DM group and the T2DM+RvD1 group were significantly higher,and the difference was statistically significant(P<0.05).Compared with the T2 DM group,the blood cholesterol(CHOL)and triglyceride(TG)levels in the mice of the T2DM+RvD1 group were reduced,and the difference was statistically significant(P<0.05).4.Detection of serum TNF-?,IL-6 levels in miceCompared with the NC group,T2 DM group and T2 DM + RvD1 mice serum TNF-?,IL-6 was significantly higher,the difference was statistically significant(P<0.05).There was no significant difference between TNF-? and IL-6 in NC group and T2DM+RvD1 group(P>0.05).After 3 weeks oftreatment with RvD1,compared with T2 DM group,the levels of TNF-? and IL-6 in serum of T2DM+RvD1 mice were decreased,and the difference was statistically significant(P<0.05).5.Changes in levels of NF-?B,IRS-1,P-IRS-1(Ser307),P-IRS-1(Tyr896),and GLUT4 protein in adipose tissue of miceCompared with NC group,P-IRS-1(Ser307)and NF-?B protein in adipose tissue of T2 DM group and T2DM+RvD1 group were significantly increased,and the difference was statistically significant(P<0.05).After treatment with RvD1 for 3 weeks,compared with T2 DM group,the above-mentioned indexes in adipose tissue of T2DM+RvD1 mice were reduced,and the differences were statistically significant(P<0.05).Compared with NC group,the levels of IRS-1,P-IRS-1(Tyr896)and GLUT4 protein in adipose tissue of T2 DM group and T2DM+RvD1 group were significantly decreased,and the difference was statistically significant(P<0.05).After treatment with RvD1 for 3 weeks,compared with T2 DM group,the above indicators in adipose tissue of T2DM+RvD1 mice were increased,and the differences were statistically significant(P<0.05).Conclusion:1.RvD1 can improve the insulin resistance of adipose tissue in type 2diabetic mice.2.RvD1 may reduce the production of TNF-?,IL-6 and other inflammatory factors by reducing the expression of NF-?B in adipose tissue,and increase the tyrosine phosphorylation level of insulin receptor substrate 1and decrease the phosphorylation level of serine.The final increase in GLUT4 expression improves insulin resistance. |
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