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Fat cells play key role in development of type 2 diabetes
Date:7/6/2010

CINCINNATICellular changes in fat tissuenot the immune systemlead to the "hyperinflammation" characteristic of obesity-related glucose intolerance and type 2 diabetes, according to new research from the University of Cincinnati (UC).

Cancer and cell biology experts say this new discovery about the cellular mechanisms behind glucose intolerance may provide a different target for drugs to treat type 2 diabetes as well as insights into how aggressive cancers form.

The study, led by Jorge Moscat, PhD, is reported in the July 7, 2010, issue of the scientific journal Cell Metabolism.

For this study, Moscat and his UC collaborator Maria Diaz-Meco, PhD, looked at the role of a specific gene known as protein kinase C (PKC)-zeta, which has been implicated as a key cellular contributor to malignant tumor growth. Using a preclinical animal model, they found that PKC-zeta had a dual role in the molecular signaling that leads to inflammation, switching from acting as a regulator of inflammation to a proinflammation agent in different circumstances.

"This finding is quite novel because current drug development efforts target immune cells (macrophages, T-cells) to eliminate this hyperinflammation. Our research suggests obesity-related glucose intolerance has nothing to do with the immune system. It may be more effective to target adipocytes (fat cells)," explains Moscat, principal investigator of the study and chair of UC's cancer and cell biology department.

In normal cells, explains Moscat, PKC-zeta regulates the balance between cellular inflammatory responses to maintain glucose control. During obesity-induced inflammation, however, the function of PKC-zeta changes and the molecule begins to promote inflammation by causing adipocytes to secrete a substance (IL-6) that travels in large quantities to the liver to cause insulin resistance.

"We believe a similar mechanism of action is at play in malignant tumor de
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Contact: Amanda Harper
amanda.harper@uc.edu
513-558-4657
University of Cincinnati Academic Health Center
Source:Eurekalert

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