S-Adenosyl-L-methionine ameliorates TNFα-induced insulin resistance in 3T3-L1 adipocytes

Abstract

An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The I κB kinase-beta (IKK-beta)/nuclear factor-κB (NF-κB) pathway is a molecular mediator of insulin resistance. S-Adenosyl-L-methionine (SAM) has both antioxidative and anti-inflammatory properties. We investigated the effects of SAM on the glucose transport and insulin signaling impaired by the tumor necrosis factorα (TNF α) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNF α. The TNFα-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. In addition, SAM significantly attenuated the TNFα-induced degradation of I κB-α and NF-κB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-beta in vitro. These results suggest that SAM can alleviate TNFα mediated-insulin resistance by inhibiting the IKK-beta/NF-κB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.