Endogenous CSE/H2 S system mediates TNF-α-induced insulin resistance in 3T3-L1 adipocytes.
Tumour necrosis factor-α (TNF- α)is a major contributor to the pathogenesis of insulin resistance associated with obesity and type 2 diabetes. It has been found that endogenous hydrogen sulfide (H2 S) contributes to the pathogenesis of diabetes. We have hypothesized that TNF-α-induced insulin resistance is involved in endogenous H2 S generation. The aim of the present study is to investigate the role of endogenous H2 S in TNF-α-induced insulin resistance by studying 3T3-L1 adipocytes. We found that treatment of 3T3-L1 adipocytes with TNF-α leads to deficiency in insulin-stimulated glucose consumption and uptake and increase in endogenous H2 S generation. We show that cystathionine γ-lyase (CSE) is catalysed in 3T3-L1 adipocytes to generate H2 S and that CSE expression and activity are upregulated by TNF-α treatment. Inhibited CSE by its potent inhibitors significantly attenuates TNF-α-induced insulin resistance in 3T3-L1 adipocytes, whereas H2 S treatment of 3T3-L1 adipocytes impairs insulin-stimulated glucose consumption and uptake. These data indicate that endogenous CSE/H2 S system contributes to TNF-α-caused insulin resistance in 3T3-L1 adipocytes. Our findings suggest that modulation of CSE/H2 S system is a potential therapeutic avenue for insulin resistance.
Department of Endocrinology, Affiliated Wuxi Second Hospital, Nanjing Medical University, Wuxi, 214002, Jiangsu, China. wxhuangcy@163.com
Ci-You
CY
Huang
Wei-Feng
WF
Yao
Wei-guo
WG
Wu
Yu-Lian
YL
Lu
Hui
H
Wan
Wen
W
Wang
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D003542:Cystathionine gamma-Lyase; D005947:Glucose; D006862:Hydrogen Sulfide