LOUISIANA RESEARCH


	Protein Promise How LSU is paving the road to a diabetes 'wonder drug' by Andrea Neighbours If Louisiana State University biochemist Dr. Jacqueline Stephens could give life and form to the test tube of mouse cells responsible for her groundbreaking research on obesity and type II diabetes, she would likely have the fattest mouse ever to walk-or more likely, collapse-on the earth. But if her discovery in the lab can be translated down the road into a new generation medication for diabetes, such a rotund rodent could be worth his weight in gold. An estimated 16 million Americans suffer from diabetes, considered the sixth leading cause of death in the United States. As many as 90 percent suffer from type II, or adult onset diabetes. Unlike type I diabetics, who cannot produce any insulin to move glucose out of the bloodstream and into the body's cells, type II diabetics do not adequately respond to the insulin their pancreas produces. Despite scientific gains in the last decade that have brought to the marketplace significant new treatments for type II diabetes, demand remains high for new therapies and a greater understanding of the way the body produces fat and responds to insulin-two integral pieces of the diabetes/obesity puzzle. Although cautious not to overstate her case, Dr. Stephens believes her research involving proteins could have an impact on the design of diabetes drugs in the future and could very well offer diabetics compelling treatment options. "Do we have a cure for diabetes? No. But any time you can understand how a protein plays a role in insulin sensitivity, you have a possible therapeutic for diabetes treatment," she says. It is known that obesity frequently triggers insulin resistance leading to type II diabetes, but the mechanism by which this occurs has long puzzled researchers. After four years in Boston researching insulin action in the body, Stephens came to Louisiana's flagship university in Baton Rouge in 1996 with a hunch that studying a certain family of proteins in cells that promote fat cell formation, called STAT proteins, might lead the way to learning how the body produces fat cells and reacts to insulin. Stephens' STAT proteins are present in the nucleus of all cells throughout the body, but she examines their activity specifically in fat cells, comparing STAT behavior in both diabetic and healthy fat cells. She compares how her STAT5 proteins respond to or act with varying levels of insulin. What her findings reveal is that STAT5 appears to be a key mediator in insulin sensitive fat cells, which has led her to hypothesize that the protein under certain conditions may be able to rehabilitate fat cells that have stopped recognizing insulin. If STAT5 proves as successful as Stephens hopes in rehabilitating fat cells and restoring the cell's ability to process insulin, the biotechnology industry may have another human protein to add to its list of "wonder drugs." Unlike typical chemical drugs like aspirin, human-protein therapeutics are man-made versions of substances the body naturally produces. One day, perhaps type II diabetes patients will be able to receive a treatment composed largely of STAT5 proteins that will help their bodies respond to insulin. Or perhaps, Stephens' research will lead her to discover an enzyme that will bind to STAT5 and keep it from producing fat. Patients then may have an opportunity, down the road, to take this mystery enzyme as a treatment in fighting obesity. Recognizing the large-scale potential of Stephens' research, the National Institute of Health in December 2003 awarded her a grant of nearly $2 million to continue her work with STATs in fat. "This is just one of several multi-million dollar grants Stephens has brought to LSU," states Dr. Kevin Smith, the university's vice chancellor for Research & Graduate Studies. "Her work is a perfect example of how basic science can contribute to the practice of medicine, potentially improving and saving the lives of many people. The NIH grant is a testament to her standing in the national scientific community and to the impact of her research on the problems associated with diabetes in Louisiana and across the country. Hers is the kind of research that can launch exciting economic development initiatives for our state in the future."