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February 25, 2004


Penn Researchers Establish Hormonal Link Between Obesity and Diabetes

(Philadelphia, PA) -- Resistin, a hormone secreted by fat cells in mice, was discovered three years ago by researchers at the University of Pennsylvania School of Medicine. Continued study of resistin in mouse models has focused on its role in glucose metabolism, obesity, and Type 2 Diabetes Mellitus. Collectively these studies point toward resistin as a new target for treatment of endocrine diseases.

The team, led by Mitchell A. Lazar, MD, PhD, Chief of the Division of Endocrinology, Diabetes, and Metabolism at Penn’s Medical Center, developed and compared a strain of mice lacking resistin with those having normal levels, to determine resistin’s role in maintaining proper levels of glucose. As the fuel that allows the body to function, it is essential to have glucose available in proper amounts. During a period of fasting - such as sleep - the liver is able to generate glucose from fats and protein. Significant differences in blood glucose levels became evident after both groups of mice fasted for periods of four hours or longer. The process was severely impaired in the mice lacking resistin, suggesting the hormone acts as a key regulator of glucose metabolism.

Remarkably, when both groups of mice were fed high fat diets, those without resistin showed a significantly lower relationship between weight and blood glucose levels. This indicates a positive correlation between the presence of resistin and insulin resistance, a reduced sensitivity by tissues to this hormone. The study appears in last week’s issue of Science.

“Circulating hormones, some only recently discovered, clearly combine to create metabolic havoc,” says Lazar. “In our modern environment, characterized by nutritional excess, these hormones may be specific targets for prevention and treatment of obesity and diabetes.”

The role of resistin in humans is sometimes questioned because it is secreted by macrophage cells in humans, rather than fat cells as in mice. However, regardless of point of origin, elevated levels of resistin are present in the obese and correlate positively with insulin resistance. In addition some drugs currently used to treat diabetes lower resistin in both mice and humans.

Future research in this area aims to establish the role of resistin in human diseases. Measurement of resistin in a simple blood test might then be useful in detecting insulin resistance and prediabetic conditions. Looking forward, counteracting resistin’s affects on the body might be a new approach to preventing and treating diabetes.

Scientists also contributing to this research include Ronadip R. Banerjee, Shamina M. Rangwala, Jennifer S. Shapiro, A. Sophie Rich, Ben Rhoades, Yong Qi, and Juan Wang at Penn; and Michael W. Rajala, Alessandro Pocal, Phillipp E. Scherer, Claire M. Steppan, Rexford S. Ahima, Silvana Obici, and Luciano Rossetti at Albert Einstein College of Medicine.

This work was funded by the National Institutes of Health and an independent Freedom to Discover Award from the Bristol-Myers Squibb Research Institute. The authors have no competing financial interest in this work.

Dr. Lazar can be contacted at 215-898-0198 or lazar@mail.med.upenn.edu.

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PENN Medicine is a $2.2 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation’s first integrated academic health system).

Penn’s School of Medicine is ranked #2 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report’s most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

Penn Health System consists of four hospitals (including its flagship Hospital of the University of Pennsylvania, consistently rated one of the nation’s “Honor Roll” hospitals by U.S. News & World Report), a faculty practice plan, a primary-care provider network, three multispecialty satellite facilities, and home health care and hospice.


Release available online at http://www.uphs.upenn.edu/news/News_Releases/feb04/lazar.htm