Enzyme Inhibition May Prevent Diabetes

Researchers studying the biochemical basis for insulin resistance and type II diabetes have found that the enzyme IkB kinase beta (IKK-beta), involved in the expression of inflammatory responses, is responsible for both local insulin resistance in the liver and more generalized resistance spread by the myeloid cells of the immune system.

To study the role of IKK-beta, investigators at the University of California, San Diego (USA; www.ucsd.edu) genetically engineered lines of mice lacking the gene for IKK-beta, either in the liver (hepatocytes) or in the immune system (myeloid cells). Both types of IKK-beta-deficient mice and a group of normal control animals were fed a high-fat diet that normally causes metabolic syndrome and type II diabetes.


Results published in the February 2005 issue of Nature Medicine showed that the normal animals developed insulin-resistant symptoms and diabetes. Mice lacking IKK-b in their liver cells retained insulin sensitivity in the liver but became insulin-resistant in fat and muscle. The mice lacking IKK-b in myeloid cells retained insulin sensitivity in all tissues.

The authors suggested that inhibition of IKK-beta, especially in myeloid cells, might be used to treat insulin resistance. "The potential for a new diabetes treatment is great,” said contributing author, Dr. Jerrold Olefsky, head of the division of endocrinology and metabolism at the University of California, San Diego. "An inhibitor of IKK-beta could be used, or an inhibitor of any other molecule in the inflammation pathway.”




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