Exendin-4 improves insulin resistance by declining expression of endoplasmic reticulum stress markers in 3T3-L1 adipocytes
10.3969/j.issn.1000-4718.2017.07.017
- VernacularTitle:Exendin-4可通过下调内质网应激信号标志蛋白表达改善3T3-L1脂肪细胞的胰岛素抵抗
- Author:
Li MA
;
Binbin GUAN
;
Linxi WANG
;
Xiaoying LIU
;
Zhou CHEN
;
Libin LIU
- Keywords:
Exendin-4;
Endoplasmic reticulum stress;
3T3-L1 adipocytes;
Insulin resistance
- From:
Chinese Journal of Pathophysiology
2017;33(7):1258-1263
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To explore the effects of exendin-4 (EX-4) on endoplasmic reticulum stress (ERS)-mediated insulin resistance in the 3T3-L1 adipocytes.METHODS: In vitro 3T3-L1 pre-adipocytes were differentiated into adipocytes, and the cells were treated with tunicamycin (TM), tauroursodeoxycholic acid (TUDCA) or EX-4, respectively.The cell viability was measured by MTT assay.The glucose consumption was determined by glucose oxidase assay to evaluate insulin sensitivity of the 3T3-L1 adipocytes with different interventions.The protein levels of p-Akt, Akt and endoplasmic reticulum stress markers, including inositol requiring enzyme-1 (IRE1), p-IRE1, JNK, p-JNK, protein kinase R-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic initation factor 2 alpha (eIF2a), p-eIF2a, activating transcription factor-6(ATF-6) were detected by Western blot.RESULTS: The insulin-stimulated glucose consumption and the protein level of p-Akt were inhibited by TM at 5 mg/L for 5 h (P<0.05), while they were increased when the cells were treated with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The effects above induced by TM (5 mg/L for 5 h) were also blunted by pretreating with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The protein levels of ERS markers such as p-IRE1, p-JNK, p-PERK, p-eIF2a and ATF-6 were significantly increased by treating with TM at 5 mg/L for 5 h, whereas 24 h pre-treatment with TUDCA or Ex-4 alleviated the ERS of the 3T3-L1 adipocytes induced by TM.The expression of total IRE1, JNK, PERK and eIF2a was not changed in different groups.CONCLUSION: Exendin-4 improves endoplasmic reticulum stress mediated insulin resistance in 3T3-L1 adipocytes.
