Pioglitazone reverses TNF-α-induced insulin resistance in 3T3-L1 adipocytes
- VernacularTitle:吡格列酮减轻肿瘤坏死因子α所致3T3-L1脂肪细胞胰岛素抵抗
- Author:
Tianshu ZENG
;
Lulu CHEN
;
Li YUAN
- Publication Type:Journal Article
- Keywords:
Protein kinase
- From:
Chinese Journal of Diabetes
2005;13(6):423-425
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether the effect of pioglitazone on TNF-α-induced insulin resistance is associated with altering IRS-1-induced signaling. Methods 3T3-L1 adipocytes were treated with TNF-α for 24 hours with or without being pretreated with 10μM piglitazone for 6 hours or with pioglitazone alone.Insulin-stimulated glucose uptake of 3T3 adipocytes was measured by using 2-deoxy 3H glucose.The Western blot was used to measure IRS-1, PKB, PKC-λ protein and tyrosine phosphorylation on IRS-1, PKB and PKC-λ phosphorylation. Results Both TNF-α and pioglitazone increased glucose uptake of 3T3 adipocytes under basal status.On TNF-α treated cells, insulin-stimulated glucose uptake was decreased by about 50%, accompanied with the reductions of IRS-1 protein level, tyrosine-phosphorylation of IRS-1 and PKB phosphorylation.TNF-α treatment had no effect on PKC-λ phosphorylation. Pioglitazone pretreatment was able to antagonize TNF-α-induced insulin resistance in 3T3 adipocytes partly reverse IRS-1 protein, increase insulin-stimulated tyrosine phosphorylation of IRS-1,and increase phosphorylations of PKB and PKCλ. Conclusion TNF-α-induced insulin resistance in 3T3-L1 adipocytes is related to impaired tyrosine phosphorylation of IRS-1. Pioglitazone antagonizes the above TNF-α induced insulin resistance.
