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Inflammatory status and insulin resistance

Grimble, Robert F.

Current Opinion in Clinical Nutrition and Metabolic Care: September 2002 - Volume 5 - Issue 5 - p 551-559

Purpose of review The inflammatory response is essential in the response to pathogens. TNF-α, IL-1 and IL-6 are key mediators of the response. They initiate metabolic changes to provide nutrients for the immune system, from host tissues. These changes include hyperlipidemia and increased gluconeogenesis. Insulin resistance and disordering of lipid metabolism occur in obesity, diabetes mellitus, atherosclerosis. This review examines recent research that links inflammation to insulin insensitivity.

Recent findings Population studies show a strong association between indices of inflammation, and abnormal lipid and carbohydrate metabolism, obesity and atherosclerosis. TNF-α is produced, by cells of the immune system and by adipocytes. It may provide the link between inflammation and insulin sensitivity. TNF-α results in insulin insensitivity, indirectly by stimulating stress hormone production and directly by sustained induction of SOCS-3 which decreases insulin-induced insulin receptor substrate 1 (IRS1) tyrosine phosphorylation and its association with the p85, regulatory subunit of phosphatidylinositol-3 kinase; and by negative regulation of PPAR gamma. Adipose tissue produces both TNF-α and leptin. Production of the latter relates positively to adipose tissue mass and through its actions on immune function exerts a pro-inflammatory influence.

Summary Recent studies on diseases which involve insulin insensitivity (e.g. obesity, type 2 diabetes and atherosclerosis) also show increased cytokine production and markers of inflammation. Evidence at present favours chronic inflammation as a trigger for chronic insulin insensitivity, rather than the reverse situation.

Institute of Human Nutrition, School of Medicine, University of Southampton, Southampton SO16 7PX, UK

Correspondence to Robert F. Grimble, Institute of Human Nutrition, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. Tel: 023 8059 4302; fax: 023 8059 4383; e-mail:

© 2002 Lippincott Williams & Wilkins, Inc.