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

• Published in: Experimental & molecular medicine 2010, 42(5), , pp.345-352
• Main Authors: Moon, Min Kyong, Kim, Min, Chung, Sung Soo, Lee, Hyun Joo, Koh, Sung Hee, Svovoda, Peter, Jung, Myung Hee, Cho, Young Min, Park, Young Joo, Choi, Sung Hee, Jang, Hak Chul, Park, Kyong Soo, Lee, Hong Kyu
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Medical Biochemistry; Molecular Medicine; Original; Stem Cells; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2010.42.5.036

An association between inflammatory processes and the pathogenesis of insulin resistance has been increasingly suggested. The IκB kinase-β (IKK-β)/ 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 factor α (TNFα) in 3T3-L1 adipocytes. SAM partially reversed the basal and insulin stimulated glucose transport, which was impaired by TNFα. 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 IκB-α and NF-κB activation. Interestingly, SAM directly inhibited the kinase activity of IKK-β in vitro . These results suggest that SAM can alleviate TNFα mediated-insulin resistance by inhibiting the IKK-β/NF-κB pathway and thus can have a beneficial role in the treatment of type 2 diabetes mellitus.