S-Adenosyl-L-methionine ameliorates TNFalpha-induced insulin resistance in 3T3-L1 adipocytes.
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.
Moon
Min Kyong
MK
Department of Internal Medicine, Eulji University School of Medicine, Seoul 139-872, Korea.
Kim
Min
M
Chung
Sung Soo
SS
Lee
Hyun Joo
HJ
Koh
Sung Hee
SH
Svovoda
Peter
P
Jung
Myung Hee
MH
Cho
Young Min
YM
Park
Young Joo
YJ
Choi
Sung Hee
SH
Jang
Hak Chul
HC
Park
Kyong Soo
KS
Lee
Hong Kyu
HK
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology* / Q000627:therapeutic use*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D012436:S-Adenosylmethionine; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase; D005947:Glucose