IKK-β links inflammation to obesity-induced insulin resistance

Speaker: 張振田                          Place: 601 room

Commentator : 呂政展 老師                           Time: 2005/o5/18 13:10-14:00  

Abstract:

   The association of obesity with type 2 diabetes mellitus (DM) has been recognized for decades, and the major basis for this link is the ability of obesity to engender insulin resistance.  Insulin resistance is a fundamental aspect of the etiology of type 2 DM and is also linked to a wide array of other pathophysiologic sequelae including hypertension, hyperlipidemia, and atherosclerosis (i.e. the metabolic syndrome).  Although insulin resistance associated with obesity is an important contributor to disease development of Type 2 DM, its underlying molecular etiology remains to be elucidated.  Previous studies revealed that obese individuals had higher levels of NF-κB -related proinflammatory cytokines, including TNF-α, IL-1β and IL-6, giving rise to the hypothesis that obesity-induced insulin resistance is an inflammatory condition.  In this study, the authors used tissue-specific knockout mice to investigate the role of IKK-β, an activator of NF-κB encoded byikbkb, in insulin resistance.  The experimental data of this study showed that mice lacking IKK-β in hepatocyte (Ikbkb^△ hep) retained liver insulin responsiveness, but still developed insulin resistance in muscle and fat in response to high fat diet, obesity or aging.  In contrast, mice lacking IKK-βin myeloid cells (Ikbkb ^△mye) retained global insulin sensitivity and were protected from insulin resistance.  Thus, IKK-β acts locally in liver and systemically in myeloid cells, where NF-κB activation induces inflammatory mediators that cause insulin resistance.  These findings demonstrate the importance of IKK-β in hepatic and systemic insulin resistance via the signal transduction pathway of NF-κB and provides a novel target of prevention and treatment of insulin resistance.

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