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Inflammation May Trigger Insulin Resistance

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Recent research suggests that insulin resistance and inflammation are linked through the actions of some inflammatory immune cells and the genes which govern them.

For some time scientists have known that there is a somewhat hyperactive immune response in people with type II diabetes mellitus, resulting in an overproduction of inflammatory immune chemicals with nothing constructive to do in the body.  Substances with mellifluous names such as TNF-alpha, pro-inflammatory cytokines and FOXO-1 became the focus of research into the causes of insulin resistance with some very interesting results.

Substances secreted by the immune cells are generally referred to as cytokines.  One of these cytokines in particular – TNF-alpha – plays a major role in inflammation and the development of disease.  Researchers at Harvard University in the early 1990′s found that rats with type II diabetes had high levels of TNF-alpha in their fatty tissues.  To learn more about the role TNF-alpha might play in diabetes, they then bred rats with obese rats which were unable to produce TNF-alpha and found that these rats did not develop diabetes.  Since then research has progressed in this area and scientists have discovered that not only TNF-alpha, but inflammation in general can activate and increase the expression of several proteins that suppress the insulin-signalling pathways, resulting in insulin resistance.

Obesity and insulin resistance are both drivers of inflammation causing a vicious cycle through a positive feedback loop.  When fat cells have grown to such an extent that the area they occupy is too overcrowded and cramped, circulation is decreased, they are unable to be properly supplied with nutrients and oxygen from the blood supply and those fat cells start to die, which attracts immune cells to the area.  When someone becomes severely insulin resistant and the pancreas can no longer keep up with the demand for insulin, the activity of a protein called FOXO-1 is increased.  Ordinarily, insulin rapidly inhibits FOXO-1 by moving it out of the nucleus of cells where it can begin to degrade.  FOXO-1 turns on the expression of another major inflammatory cytokine – interleukin 1-beta – which interferes in the insulin signalling pathway.

It is not yet known whether inflammation precedes insulin resistance or vice versa or whether both pathways are possible.  In the interim, it would seem sensible for those with insulin sensitivity issues, to do everything they can to lower their inflammation levels.  Blood tests such as C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR) can help monitor progress in this area.  Stress-reduction through such activities as meditation, physical exertion, listening to music or simply having some “me” time are vital.  Fresh fruit and vegetables, omega 3 fatty acids and ginger are also potent anti-inflammatory agents.

More Information:

Chronic Subclinical Inflammation as Part of the Insulin Resistance Syndrome The Insulin Resistance Atherosclerosis Study (IRAS) Andreas Festa, MD; Ralph D’Agostino, Jr, PhD; George Howard, DrPH; Leena Mykkänen, MD, PhD; Russell P. Tracy, PhD; Steven M. Haffner, MD Circulation 2000;102;42-47

http://circ.ahajournals.org/cgi/reprint/102/1/42

Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance Haiyan Xu, Glenn T. Barnes, Qing Yang, Guo Tan, Daseng Yang, Chieh J. Chou, Jason Sole, Andrew Nichols, Jeffrey S. Ross, Louis A. Tartaglia and Hong Chen J Clin Invest. 2003;112(12):1821–1830 doi:10.1172/JCI19451

http://www.jci.org/articles/view/19451/version/1

Inflammation, Insulin Resistance, and Adiposity: A study of first-degree relatives of type 2 diabetic subjects Adamandia D. Kriketos, Jerry R. Greenfield, Phil W. Peake, PHD3, Stuart M. Furler, Gareth S. Denyer, John A. Charlesworth, Lesley V. Campbell Diabetes Care August 2004 vol. 27 no. 8 2033-2040

http://care.diabetesjournals.org/content/27/8/2033.full

Recent advances in the relationship between obesity, inflammation, and insulin resistance Jean-Philippe Bastard, Mustapha Maachi, Claire Lagathu, Min Ji Kim, Martine Caron, Hubert Vidal, Jacqueline Capeau, Bruno Feve Eur. Cytokine Netw., Vol. 17 n° 1, March 2006, 4-12

http://www.john-libbey-eurotext.fr/e-docs/00/04/18/09/vers_alt/VersionPDF.pdf

Inflammation and insulin resistance Steven E. Shoelson, Jongsoon Lee, Allison B. Goldfine J Clin Invest 2006;116(7):1793–1801 doi:10.1172/JCI29069

http://www.jci.org/articles/view/29069/version/1/pdf

IKK-beta links inflammation to obesity-induced insulin resistance  Melek C Arkan, Andrea L Hevener, Florian R Greten, Shin Maeda, Zhi-Wei Li, Jeffrey M Long, Anthony Wynshaw-Boris, Giuseppe Poli, Jerrold Olefsky & Michael Karin Nature Medicine 11, 191 – 198 (2005) Published online: 30 January 2005; | doi:10.1038/nm1185

http://www.nature.com/nm/journal/v11/n2/abs/nm1185.html

Inflammation: The Link Between Insulin Resistance, Obesity and Diabetes Paresh Dandona, Ahmad Aljada and Arindam Bandyopadhyay Trends in Immunology Volume 25, Issue 1, January 2004, Pages 4-7

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6W7H-49YH899-1&_user=10&_coverDate=01%2F31%2F2004&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1647382311&_rerunOrigin=scholar.google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ddb3e815e048e61a99a32958b07f0e5e&searchtype=a

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