Role of inflammation in the pathogenesis of insulin resistance

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Abstract

The evidence linking inflammation and diabetes dates back more than a century to the finding that treatment with high-dose sodium salicylate decreased glycosuria in patients presumed to have type 2 diabetes (for review see Ref. 1). Additional studies in the late 1950s further established a possible role for inflammatory processes in the etiology of diabetes and insulin resistance (2,3). However, the concept that inflammation may be critical to the pathogenesis of diabetes was not appreciated until Hotamisligil and colleagues (4) made the seminal observation that proinflammatory cytokines such as TNFwere highly expressed within adipose tissue and could significantly contribute to insulin resistance. Specifically, it was shown that administration of a neutralizing anti-TNF receptor-IgG chimera to genetically obese fa/fa rats improved insulin sensitivity (4). In addition, genetically obese ob/ob mice with targeted mutations in both p55 and p75 TNF receptors, and hence unresponsive to the effects of TNF, display an improved insulin sensitivity relative to ob/ob mice expressing fully functional alleles encoding the p55 and p75 TNF receptors (5). These studies stimulated a paradigm shift in our understanding of the nature of metabolic disease and were a harbinger for a new field of research that has subsequently characterized many aspects of the relationship between inflammation and metabolic disease.

Original languageEnglish
Title of host publicationDiabetes
Subtitle of host publicationTranslating Research into Practice
PublisherCRC Press
Pages57-74
Number of pages18
ISBN (Electronic)9781420047363
ISBN (Print)1420043714, 9781420043716
Publication statusPublished - 1 Jan 2008
Externally publishedYes

Cite this

Lancaster, G. I., Hevener, A., & Febbraio, M. A. (2008). Role of inflammation in the pathogenesis of insulin resistance. In Diabetes: Translating Research into Practice (pp. 57-74). CRC Press.