ABSTRACT
Objective:To investigate the effects of Exendin-4 (Ex-4) on the expressions of lipid metabolism related genes in the human liver cancer HepG2 cells with insulin resistance (IR),and to elucidate the effect of Ex-4in improvement of IR.Methods:The HepG2 cells in logarithmic growth phase were induced into IR model with high concentration of insulin,then divided into control group (HepG2 cells),IR group (HepG2 cells were treated with insulin,HepG2-IR cells),and Ex-4 group (HepG2-IR cells were treated with Ex-4).Glucose oxidase (GOD-POD)kit was used to detect the consumption of glucose.The cell morphology and intracellular lipid drip formation were observed by Oil red O staining.The triglyceride (TG) level in cells was detected by kit;qRT-PCR was used to detect the mRNA expression levels of acetyl-CoA carboxylase (ACC),fatty acid synthase (FAS),sterol regulatory element-binding protein-1c (SREBP-1c) and apolipoprotein B100 (apoB100).Results:Compared with control group (HepG2 cells),the glucose consumption in the HepG2-IR cells in IR group was significantly decreased (P＜0.01).Compared with IR group,the glucose consumption in the HepG2-IR cells in Ex-4 group was increased (P＜0.05).The Oil O red staining results showed that compared with control group,the fat percentage in the HepG2-IR cells in IR group was increased (P＜0.05);compared with IR group,the fat percentage in Ex-4 group was decreased (P＜0.05).Compared with control group,the level of TG in the cells in IR group was significantly increased (P＜0.01);compared with IR group,the level of TG in the cells in Ex-4 group was significantly decreased (P＜0.05).The qT-PCR results showed that compared with control group,the expression levels of ACC FAS and SREBP-1cmRNA in the cells in IR group were increased (P＜0.01),and the expression level of apoB100 mRNA was decreased (P＜0.05);compared with IR group,the expression levels of ACC,FAS and SREBP-1c mRNA in the cells in Ex-4 group were decreased (P＜0.05),and the expression level of apoB100 mRNA was increased (P＜0.01).Conclusion:Ex-4 can regulate the expressions of lipid metabolism related genes in the HepG2 cells and improve IR.
ABSTRACT
Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB)on the blood glucose homeostasis,insulin resistance and inflammation of the obese type 2 diabetic (T2DM)ZDF rats,and to discuss its possible mechanism.Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n = 10).There were 8 rats survived in each group after operation.The level of blood glucose (FBG)was detected by Roche glucose meter at 1 week before operation,2 weeks,4 weeks and 6 weeks after operation;the fasting serum insulin level of the rats was measured by ELISA kit;the insulin sensitivity index (HOMA-ISI)and insulin resistance index (HOMA-IR)were calculated.The rats were executed 6 weeks after operation.HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats;the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β(IL-1β),interleukin 6 (IL-6),tumor necrosis factorα(TNF-α),nuclear factorκB (NF-κB),and interleukin 10 (IL-10)mRNA of the rats were detected by QRT-PCR method.Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased (t=3.798,P <0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205,P <0.05).Six weeks after operation,compared with sham operation group,the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441,P <0.05)and the HOMA-ISI was significantly increased (t=-8.65,P < 0.05).The HE staining results showed that compared with sham operation group,the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β,IL-6,TNF-αand NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P < 0.05), while the expression level of IL-10 was significantly increased (P < 0.05).The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group.Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats,and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.