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EXPERIMENTING
WITH DRUGS Roughly 18.2 million people in the U.S. have diabetes. According to the National Institutes of Health, diabetes was the primary cause of death listed on 69,301 death certificates in the U.S. in 2000. More than 1,700 people died in 2002 from complications caused by diabetes according to the 2002 Louisiana Health Report Card issued by the Louisiana Department of Health and Hospitals, making diabetes one of Louisiana’s top five causes of death.
Now in her seventh consecutive year of funding from the American Diabetes Association, biologist Jackie Stephens is studying how the PPAR-gamma protein, short for peroxisome proliferators-activated receptor, is regulated and turned over in fat cells. PPAR-gamma is a nuclear hormone receptor that is responsible for mediating the expression of fat-specific genes. Many patients with type II diabetes have altered levels of PPAR-gamma expression. Moreover, many type II diabetes patients are currently being treated with a compound called thiazolidindione, or Avandia®, as it is commonly known. The compound activates the PPAR-gamma protein and eliminates it from the cell. Beth Floyd, a postdoctoral fellow of the American Heart Association, who is working with Stephens, has examined how a variety of stimuli regulate this degradation process. These studies are clinically relevant because studies in mice have demonstrated that having less PPAR-gamma protein in some cells can reverse insulin resistance, a hallmark condition of type II diabetes. "By
better understanding the regulation of PPAR-gamma proteins under
different conditions, we can gain insight into the pathogenesis
of obesity and type II diabetes. Hopefully, our research will
facilitate the development of drugs that could help patients with
a wide range of metabolic disorders," says Stephens.
"Our results are significant because they demonstrate that the cellular machinery that causes protein degradation can contribute to the pathogenesis of insulin resistance,” says Stephens. “There is very little information known about how this pathway contributes to diabetes. Hence, these studies are very novel and will shed new light on how to treat diabetes in the future." ON
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By
discovering ways to understand how current drugs work at the cellular
level, one LSU researcher is performing experiments that may have
a significant impact on the lives of diabetes patients.
Stephens
and her team of seven, including postdoctoral researchers, research
associates, and both graduate and undergraduate students, are
working to understand how diabetes drugs can have different effects
on protein components and be regulated.