Effect And Mechanisms Of Exendin-4on Endoplasmic Reticulum Stress Mediated Insulin Resistance In3T3-L1Adipocytes

AIM: Insulin resistance is closely related with Endoplasmic Reticulum stress（ERs）.So In this study we adopted endoplasmic reticulum stress inducertunicamycin induced insulin resistance in3T3-L1adipocytes. In addition, we studiedthe effect of Exendin-4and Tauroursodeoxycholic Acid as a positive control oninsulin stimulated glucose consumption in3T3-L1adipocytes and the expression ofERs related protein (p-IRE-1a,IRE-1a,p-JNK,JNK). Preliminary study the effect andmechanisms of Exendin-4on endoplasmic reticulum stress mediated insulinresistance in3T3-L1adipocytes.METHODS: In vitro3T3-L1pre-adipocytes were differentiated intoadipocytes.Cell viability was determined by MTT assay. Glucose oxidase (GOD)assay was used to detecte the glucose consumption and evaluated the insulinsensitivity in different intervention in3T3-L1adipocytes. The expression of the keyendoplasmic reticulum stress signaling proteins (p-IRE,p-JNK,IRE,JNK) weredetected by Western blot.RESULTS:(1) Exendin-4, in coordination with insulin, augmentedinsulin-stimulated glucose consumption in3T3-L1adipocytes by36.7%(P<0.05).Tunicamycin (5ug/ml for5h) inhibited insulin-stimulated glucose consumption by19.7%(P<0.05). After intervention by1mmol/L Tauroursodeoxycholic Acid or100nmol/L Exendin-4for24h, the inhibition of Tunicamycin could be partlyrelieved(P<0.05).(2) Western Blot showed that Tunicamycin(5ug/ml for5h) couldsignificantly increase the expression of p-IRE and p-JNK while pretreatment of3T3-L1adipocytes with1mmol/L Tauroursodeoxycholic Acid or100nmol/LExendin-4for24h could reduce the expression of p-IRE and p-JNK. The expressionof IRE and JNK was not changed in different groups.CONCLUSIONS: Endoplasmic reticulum stress can induce insulin resistancein3T3-L1adipocytes. Alleviating the endoplasmic reticulum stress can improve insulin resistance. The molecular mechanisms of Exendin-4’s improvement on insulinresistance in3T3-L1adipocytes may be related with the ease of endoplasmicreticulum stress.