Exp Mol Med.  2010 May;42(5):345-352. 10.3858/emm.2010.42.5.036.

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

• Moon MK
• Kim M
• Chung SS
• Lee HJ
• Koh SH
• Svovoda P
• Jung MH
• Cho YM
• Park YJ
• Choi SH
• Jang HC
• Park KS
• Lee HK

• KMID: 946634
• DOI: http://doi.org/10.3858/emm.2010.42.5.036

Abstract

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

Keyword

diabetes mellitus, type 2; inflammation; insulin resistance; IkappaB kinase; NF-kappaB; S-adenosylmethionine