University of Pennsylvania Health System, Pa.

Hello, my name is Mitch Lazar, and I am an endocrinologist and physician-scientist at the University of Pennsylvania in Philadelphia. I would like to tell you about the diabetes research mission of our Institute for Diabetes, Obesity, and Metabolism.

There are two major kinds of diabetes -- type 1 and type 2. These diseases have many of the same devastating complications but different causes. Type 1 diabetes is caused by destruction of the cells of the pancreas that produce the hormone insulin. Here at Penn, Ali Naji and his colleagues are working out new ways to transplant pancreatic islets to fight and even cure this disease. The battle isn't simple; and Institute scientists are working out new ways to protect these insulin-producing beta cells from rejection by the immune system.

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Another challenge is there are not enough of these cells available to transplant. Institute scientists Claus Koestler and Doris Stoffers are studying how the beta cells develop in the first place, to come up with new ideas about how to make and even regenerate these cells.

The studies don't stop at the test tube. Physician-scientists at the Institute are actively translating our basic science discoveries into treatments at the Penn Rodebaugh Diabetes Center, which provides a team approach to state-of-the-art diabetes care. Patients are given specialized tests called 'glucose clamps' in which their production of insulin and other hormones that regulate blood sugar is monitored to assess how their transplant is holding up and whether additional therapy might improve their condition.

The other type of diabetes is tied into the epidemic of obesity that is perhaps the No. 1 health threat to the industrialized world. Being overweight affects the body's ability to handle sugar, so that we are facing a twin epidemic of type 2 diabetes. The simplest solution to obesity would be for everyone to eat healthfully and to exercise regularly; but in practice people find this extremely difficult to maintain. As we continue to make every effort to modify lifestyle, we need to simultaneously understand not only why fat accumulates but why it also has such nasty effects on metabolism. Our Institute scientists, including in my own laboratory, are learning that fat cells make harmful factors that raise blood sugar. One of these is a newly recognized hormone called resistin, which was discovered here at Penn in animal models of diabetes. Resistin and other fat-derived molecules regulate how insulin works as well as the body's metabolism and even the brain's control of appetite. These discoveries are leading to new concepts and new therapies for obesity and for the diabetes that it causes.

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