Jorge Moscat Cincinnati

Glucose intolerance commonly referred to as pre-diabetes seems to occur in an innumerable amount of people. On the other hand, type 2 diabetes is known as a metabolic disorder along with revealing high blood glucose. A recent research commenced by the University of Cincinnati (UC) apparently reveals that cellular changes in fat tissue and not in the immune system cause ‘hyperinflammation’ characteristic of obesity-related glucose intolerance and type 2 diabetes.

According to the cancer and cell biology experts, the research findings about the cellular mechanisms behind glucose intolerance give a different target for drugs to treat type 2 diabetes. The investigation also seems to offer insights into the way aggressive cancers form.

Jorge Moscat, PhD principal investigator of the research and chair of UC’s cancer and cell biology department quoted, “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).”

In order to conduct the research, the scientists examined the role of the gene termed as protein kinase C (PKC)-zeta. This protein has been apparently associated with a key cellular contributor to malignant tumor growth. Having employed a preclinical animal model, the researchers were possibly able to determine the dual role played by PKC-zeta.

PKC-zeta may not only act in molecular signaling that leads to inflammation, but in different circumstances also switches from acting as a regulator of inflammation to a proinflammation agent. The researchers mentioned that the PKC-zeta regulates the balance between cellular inflammatory responses to maintain glucose control in normal cells.

Moscat said, “We believe a similar mechanism of action is at play in malignant tumor development. Now we are trying to understand how PKC-zeta regulates IL6 to better determine how we can manipulate the protein to help prevent diabetes and cancer.”

But when an obesity-induced inflammation occurs, the function of PKC-zeta is supposedly changed. The molecules seem to begin promoting inflammation by making adipocytes secrete a substance (IL-6) that is believed to travel in large quantities to the liver and cause insulin resistance.

Currently Moscat and his team are working with investigators at UC’s Drug Discovery Center to screen compounds that may restrict PKC-zeta. Potential compounds are ascertained to be employed in further investigations.

The research was published in the July 7, 2010 issue of the scientific journal Cell Metabolism.