Endogenous CSE/H2S system mediates TNF--induced insulin resistance in 3T3-L1 adipocytes

Tumour necrosis factor- (TNF- )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 (H2S) contributes to the pathogenesis of diabetes. We have hypothesized that TNF--induced insulin resistance is involved in endogenous H2S generation. The aim of the present study is to investigate the role of endogenous H2S in TNF--induced insulin resistance by studying 3T3-L1 adipocytes. We found that treatment of 3T3-L1 adipocytes with TNF- leads to deficiency in insulin-stimulated glucose consumption and uptake and increase in endogenous H2S generation. We show that cystathionine -lyase (CSE) is catalysed in 3T3-L1 adipocytes to generate H2S and that CSE expression and activity are upregulated by TNF- treatment. Inhibited CSE by its potent inhibitors significantly attenuates TNF--induced insulin resistance in 3T3-L1 adipocytes, whereas H2S treatment of 3T3-L1 adipocytes impairs insulin-stimulated glucose consumption and uptake. These data indicate that endogenous CSE/H2S system contributes to TNF--caused insulin resistance in 3T3-L1 adipocytes. Our findings suggest that modulation of CSE/H2S system is a potential therapeutic avenue for insulin resistance. Copyright (c) 2012 John Wiley & Sons, Ltd.