Penn doc unlocks diabetes

The mechanisms involved in diabetes -- a disease that plagues 16 million Americans -- form a complex puzzle that has consumed the time of researchers for decades. Mitchell Lazar, director of the Penn Diabetes Center, may have found a key to unlock a part of that puzzle. Lazar and his team recently discovered a hormone that promotes insulin resistance, the condition that leads to type 2 diabetes, the most common form of the disease. Their work appeared in this month's issue of Nature. "The cool thing for me, as an endocrinologist, is that we found it," Lazar said of the hormone, called resistin. Since it is produced in fat cells, resistin is overly present in obese patients. According to the American Diabetic Association, 80 percent of patients with type 2 diabetes are also obese. "In the U.S. there are a couple of parallel epidemics," Lazar said. "One is obesity, the other is diabetes." Lazar found that resistin levels, and thus the severity of insulin resistance, are decreased by a class of diabetes drugs known as TZDs. It was previously known that TZDs acted on fat cells, but it was not known what was the direct effect of the drugs. "[We knew that] insulin resistance is caused by fat cells," Lazar said. "Three years ago I decided the most interesting question at the time [was] how TZDs [improved] insulin resistance." Through a cellular signal, TZDs inhibit the production of resistin. With this knowledge, Lazar's team moved on to the second phase of their project. "We treated mice that had diet-induced diabetes with antibodies against resistin," Lazar explained. Through this technique the team was able to demonstrate that resistin directly promoted type 2 diabetes. Lazar's findings represent a revolution in the field, according to Allen Spiegel, director of the National Institute of Diabetes and Digestive and Kidney Diseases. "I don't think it's an exaggeration to say this is a blockbuster paper with potentially major clinical impact," Spiegel said in a statement. "In one fell swoop, Lazar and colleagues have... provided a key link between obesity and type 2 diabetes." Spiegel's institution is the part of the National Institutes of Health that funded the research. Ron Margolis, who oversaw Lazar's grant, stressed that the findings have particular significance for children. "We've begun to see a fairly large increase [of type 2 diabetes] in children because of obesity," he said, explaining that children with type 2 diabetes will be a population that will benefit significantly from Lazar's study. Despite the excitement, those involved and familiar with the research point out that there is a lot more work to be done. "We have identified the human resistin gene, but our methods and assays are designed for mice," Lazar said. "We need to develop sensitive, specific and rapid assays for human resistin." This is a task Lazar looks forward to taking on. "One of the great things about Penn is access to patients," he said. How resistin causes insulin resistance is also a question that has been left unanswered. "One of the important discoveries that's yet to be made is the receptor for insulin," Margolis said. Still, Lazar, while looking to the future, is satisfied with his discovery. "Until now, no one knew about resistin," he said. "It's a new player in a field [that was] desperate for a new player." Type 2 diabetes, which is more common in minorities, accounts for about 90 percent of diabetes in the United States.