JNK mediates TNF-α or H_2O_2-induced insulin resistance in 3T3-L1 adipocytes
- VernacularTitle:JNK介导TNF-α和H_2O_2引起的脂肪细胞胰岛素抵抗
- Author:
Honghui GUO
;
Wenhua LING
- Publication Type:Journal Article
- Keywords:
Adipocytes;
c-Jun NH_2-terminal kinase;
Insulin resistance;
Oxidative stress;
Tumor necrosis factor
- From:
Chinese Journal of Pathophysiology
2010;26(2):349-352
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To study the role of c-Jun NH_2-terminal kinase (JNK) in the development of insulin resistance induced by tumor necrosis factor-α (TNF-α) or H_2O_2 in 3T3-L1 adipocytes. METHODS: Differentiated 3T3-L1 adipocytes were pretreated with JNK1 small interfering RNA (siRNA) or JNK inhibitor SP600125, then exposed to 1 nmol/L of TNF-α or micromolar H_2O_2 generated by adding glucose oxidase (50 U/L) to the medium for 12 h. The cellular glucose uptake was determined by radioactive method. RESULTS: Compared to control adipocytes, 12 h incubation with TNF-α or H_2O_2 led to 50%-55% reduction (P<0.01) of the insulin-dependent glucose uptake. JNK1 siRNA transfection significantly inhibited JNK1 expression and blocked the TNF-α or H_2O_2-induced impairments of cellular glucose uptake. Pretreatment with SP600125 (20 μmol/L) resulted in significant increases in insulin-stimulated glucose uptakes in both TNF-α (66%) and H_2O_2 (62%) treated adipocytes (P<0.01). CONCLUSION: JNK plays a key role in TNF-α or H_2O_2 induced insulin resistance in 3T3-L1 adipocytes, and inhibition of JNK over-activation may be a new therapeutic target for insulin resistance.
