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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.
For
a printer friendly version of this release, click
here.
# # #
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
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most recent ranking of top research-oriented medical
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