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IkB kinase beta, a pro-inflammatory enzyme linked to type 2 diabetes


An enzyme that initiates inflammation has been directly linked to insulin resistance and resulting type II diabetes by researchers at the University of California, San Diego ( UCSD ) School of Medicine.
In addition, researchers suggest that inhibition of the enzyme in the immune system’s macrophages may be a new diabetes therapy.

The study describes research in mice that identifies enzyme IkB kinase beta ( Ikk-beta ) as a central coordinator of inflammatory responses in the liver and macrophages, the immune system cells which attack infections.

Both control mice and mice with Ikk-beta deleted in specific types of cells were fed a high-fat diet that normally causes metabolic syndrome and type II diabetes. While the control mice developed the diabetes and insulin-resistant symptoms, mice in which the Ikk-beta was deleted from microphages retained their healthy insulin levels.

“ The potential for a new diabetes treatment is great,” said one of the study’s senior authors, Jerrold Olefsky, chief of UCSD. “ An inhibitor of Ikk-beta could be used, or an inhibitor of any other molecule in the inflammation pathway.”

Affecting 18.2 million Americans, diabetes is a disease in which the body does not produce or properly use insulin, a hormone necessary to convert sugar, starches and other food into energy needed for daily life. Previous studies in the past few years have implicated inflammation as playing a role in diabetes, but just how this occurred was unknown.

The researchers generated mice without Ikk-beta in liver cells that play a direct role in insulin-regulated glucose metabolism, and in systemic myeloid cells, pivotal players in inflammatory responses as they produce macrophages.

In response to challenges with a high-fat diet, mice with Ikk-beta deficient myeloid cells retained insulin sensitivity in all target tissues. Because the myeloid cells ( and their macrophages ) are systemic – able to travel throughout the body – they were identified by the researchers as the best target for diabetes treatments.

The mice lacking Ikk-beta only in the liver retained their insulin sensitivity in the liver but became insulin resistant in fat and muscle.

Source: Nature Medicine, 2005

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