-the Impact Of Imatinib On Insulin Sensitivity

Aim:To investigate the effect of Gefitinib on insulin sensitivity in rats of diabetes and its mechanism.Methods:Normal Wistar rats were fed with high sucrose-fat diet for 1 month and then injected intraperitoneally with streptozotocin(STZ).The rats satisfying the definity of diabetes were divided into 3 groups and given control solution(distilled water),12.5mg/kg of Gefitinib and 25mg/kg of Gefitinib for 8 days,respectively.Body weights,FBG and FINS were recorded before,just after and 7 days after administration,respectively.Executed the rats and reserved the livers.Compared the expression of insulin receptor substrate-1(IRS-1) mRNA and phosphatidylinositol-3-kinase(PI3K) mRNA in liver among the 3 groups with semi-quantitative Reverse Transcription-Polymerase Chain Reaction(PCR).Results:Animal models were established successfully.The changes of FBG had no significant differences among the 3groups.After administration,insulin sensitivity index(ISI) of Gefitinib groups were significantly increased compared with control group.There were no significant difference between the two dose groups.7 days after administration,the improved ISI did not change.Body weights of the 3 goups had no obvious difference.The expression of IRS-1 mRNA significantly decreased in Gefitinib groups compared with control group with no obvious difference between the two dose groups,while the expression of PI3K mRNA obviously increased in Gefitinib groups compared with control group also with no obvious difference between the two dose groups.Conclusions:Gefitinib couldnot decrease FBG but could improve insulin sensitivity in rats of diabetes.2 t_1/2 after administration,the effect still existed.The effect probably due to the increase of PI3K/Akt pathway of insulin signaling,and had no relationship with body weight.