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Horm Metab Res 2010; 42(9): 632-636
DOI: 10.1055/s-0030-1255033
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Metformin Attenuates Production of Nitric Oxide in Response to Lipopolysaccharide by Inhibiting MyD88-Independent Pathway

Y. Kato1 , N. Koide2 , T. Komatsu2 , G. Tumurkhuu2 , J. Dagvadorj2 , K. Kato1 , T. Yokochi2
  • 1Department of Internal Medicine, Division of Endocrinology, Metabolism and Diabetes, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
  • 2Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan
Further Information

Publication History

received 24.12.2009

accepted 03.05.2010

Publication Date:
17 June 2010 (online)

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Abstract

Metformin is reported to ameliorate inflammation in diabetic patients. The effect of metformin on lipopolysaccharide-induced nitric oxide production was studied by using RAW 264.7 macrophage-like cells. The action of metformin was analyzed by dividing lipopolysaccharide signaling into the MyD88-dependent and -independent pathways. Metformin significantly reduced the expression of an inducible type of nitric oxide synthase and inhibited lipopolysaccharide-induced nitric oxide production. On the other hand, metformin did not inhibit lipopolysaccharide-induced tumor necrosis factor-α production. The expression levels of interferon-β protein and mRNA, which is a key molecule in MyD88-independent pathway, were significantly inhibited by metformin. Compound C, a specific AMP-activated protein kinase inhibitor, did not affect the inhibitory action of metformin. Metformin was suggested to inhibit lipopolysaccharide-induced nitric oxide production via inhibition of interferon-β production in MyD88-independent pathway. Metformin might exhibit an anti- inflammatory action on diabetic complications as well as the antidiabetic action.

Key words

lipopolysaccharide - interferon-β - metformin - MyD88-independent pathway - nitric oxide

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Correspondence

Y. KatoMD, PhD 

Department of Internal Medicine

Division of Endocrinology,

Metabolism and Diabetes

Aichi Medical University School

of Medicine

Nagakute

Aichi 480-1195

Japan

Phone: +81/561/62 3311

Fax: +81/561/63 1098

Email: ykato4@aichi-med-u.ac.jp