Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease

Diabetes Obes Metab. 2013 Sep;15 Suppl 3(0 3):117-29. doi: 10.1111/dom.12161.


Inflammation is an established pathogenic player in insulin resistance, islet demise and atherosclerosis. The complex interactions between cytokines, immune cells and affected tissues result in sustained inflammation in diabetes and atherosclerosis. 12- and 15-lipoxygenase (LO), such as 12/15-LO, produces a variety of metabolites through peroxidation of fatty acids and potentially contributes to the complex molecular crosstalk at the site of inflammation. 12- and 15-LO pathways are frequently activated in tissues affected by diabetes and atherosclerosis including adipose tissue (AT), islets and the vasculature. Moreover, mice with whole body and tissue-specific knockout of 12/15-LO are protected against insulin resistance, hyperglycaemia and atherosclerosis supporting functional contribution of 12- and 15-LO pathways in diabetes and atherosclerosis. Recently, it has emerged that there is a temporal regulation of the particular isoforms of 12- and 15-LO in human AT and islets during the development of type 1 and type 2 diabetes and obesity. Analyses of tissues affected by diabetes and atherosclerosis also implied the roles of interleukin (IL)-12 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1) in islets and IL-17A in atherosclerosis. Future studies should aim to test the efficacy of inhibitions of these mediators for treatment of diabetes and atherosclerosis.

Keywords: 12-lipoxygenase; 15-lipoxygenase; NADPH oxidase-1; interleukin-12; interleukin-17A.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adipose Tissue / physiology
  • Animals
  • Arachidonate 12-Lipoxygenase / physiology
  • Arachidonate 15-Lipoxygenase / physiology
  • Cytokines / physiology*
  • Humans
  • Inflammation / physiopathology*
  • Inflammation Mediators / physiology
  • Insulin Resistance / physiology*
  • Islets of Langerhans / physiopathology*
  • Mice
  • Vascular Diseases / physiopathology*


  • 12-15-lipoxygenase
  • Cytokines
  • Inflammation Mediators
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase