TNF-? impairs glucose uptake and IRS-1 associated signaling pathway by stimulated insulin in 3T3-L1 adipocytes
- VernacularTitle:肿瘤坏死因子?对3T3-L1细胞葡萄糖摄取和IRS-1信号通路的影响
- Author:
Tianshu ZENG
;
Li YUAN
;
Lulu CHEN
- Publication Type:Journal Article
- Keywords:
Tumor necrosis factor-?;
Insulin receptor substrate-1;
Protein kinase B;
3T3-L1 adipocyte;
Glucose uptake
- From:
Chinese Journal of Immunology
2000;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate glucose uptake and IRS-1-associated signaling pathway by stimulated insulin under TNF-? treatment.Methods:3T3-L1 adipocytes were treated with TNF-? within 6 hours and 24 hours respectively. 2-deoxy ~3H glucose was used to measure glucose uptake and western blot was used to measure IRS-1, PKB protein, tyrosine and serine307 phosphorylation on IRS-1, and PKB phosphorylation.Results:On basal status, glucose uptake of 3T3-L1 cells and phospho-tyrosine of IRS-1, PKB phosphorylation, and serine307 phosphorylation on IRS-1 were all low. Insulin stimulation induced glucose uptake and IRS-1 tyrosine phosphorylation, serine307 phosphorylation, PKB phosphorylation rapidly. TNF-? inhibited insulin-induced glucose uptake, tyrosine phosphorylation of IRS-1 and PKB phosphorylation. Rapamycin reversed the effects of TNF-?. Treated with TNF-? within 6 hours increased serine307 phosphorylation but had no effect on IRS-1 protein level. TNF-?-induced serine307 phosphorylation of IRS-1 was not affected by rapamycin. IRS-1 level was decreased under 24 hours TNF-? treatment and rapamycin can reverse the effect.Conclusion:TNF-? induced insulin resistance in 3T3-L1 adipocytes mightbe related to impaired IRS-1 tyrosine phosphorylation, rapamycin could reverse the effects of TNF-?. Treated with TNF-? within 6 hours stimulate phosphrylation of serine307 of IRS-1 and 24 hours treatment decreased IRS-1 protein level. Rapamycin antagonist TNF-?-induced loses of IRS-1.
