New Findings -
Insulin resistance, age-associated diseases
Newswise — Metabolic syndrome, an
aging-associated group of disorders that includes insulin
resistance, heart disease and high lipid levels, may be treatable
thanks to a newly discovered role for a regulatory gene, according
to a team of scientists at the Burnham Institute for Medical
Research.
In addition, the scientists found
that this single gene may contribute to the body’s responses to
caloric restriction and may explain some aspects of the Atkins Diet.
The gene’s new function was
discovered in Drosophila fruit flies; previously it was associated
solely with the control of growth. Until now, how the gene regulates
insulin, as well as other symptoms of metabolic syndrome, was
largely unknown.
The study was conducted by Sean
Oldham, Ph.D., assistant professor, and his colleagues at the
Burnham and the National Institute on Alcoholism and Alcohol Abuse.
Oldham’s findings appear in the journal Cell Metabolism to be
released on August 8th.
Using fruit flies bred with a
newly created mutant form of the gene TOR (short for target of
rapamycin), Oldham and his colleagues were able to determine how the
TOR pathway interacted with other important regulators of insulin,
glucose and lipid metabolism.
TOR is an ancient gene, found in
nearly all animal and plant cells. The researchers discovered that
their new mutant fly reduced TOR function, allowing them to observe
what happens when TOR’s influence is removed.
Reductions in TOR function lowered
glucose and lipid levels in the body. They also blocked the function
of another important insulin regulator, a factor called FOXO, which
is known to be a critical mediator of insulin signals and therefore
glucose and lipid metabolism. In addition, flies with the mutated
form of TOR had longer life spans than control flies.
“It has been unclear how TOR
signaling affects the insulin pathway,” said Oldham. “Our study adds
another dimension to TOR’s activity by revealing unexpected and
novel levels of beneficial regulation of insulin metabolism, by
reducing insulin resistance. This study provides the first details
of how TOR may regulate energy homeostasis and responses to aging,
in particular the coordination of weight reduction effects caused by
caloric restriction and, in humans, it may explain the effects of
the Atkins diet. It suggests that reducing TOR function could lead
to a possible treatment for any or all symptoms of metabolic
syndrome and insulin resistance.”
Oldham’s group, in collaboration
with Dr. Rolf Bodmer at Burnham, showed that reducing TOR function
also blocks the age-dependent decline of heart function, providing a
partial explanation for why excess calories from overeating can lead
to resistance to insulin’s ability to process sugars and may
contribute to reduced heart function.
Dr. Oldham and his colleagues are continuing their search to
understand how TOR mediates caloric restriction, aging and other
effects on insulin signaling and metabolism. They want to understand
TOR’s role in the relationship between growth, metabolism and aging,
both in healthy individuals and individuals with metabolic diseases.
The researchers also are screening possible drugs that could treat
metabolic syndrome by reducing TOR function.
“This study provides the first
direct evidence that reducing TOR function could be clinically
beneficial to counter insulin resistance, metabolic syndrome and
diabetes,” said Oldham. “We believe further studies on fruit flies
are invaluable to discovering more details about this pathway, and
will give us indispensable insight into pathological aspects of
aging and senescence.”
This study was supported by a
grant from the National Heart Lung and Blood Institute of the
National Institutes of Health, and with support from The Fishman
Fund.
About Burnham Institute for
Medical Research. The Burnham Institute for Medical Research,
founded in 1976, is an independent not-for-profit biomedical
research institution dedicated to advancing the frontiers of
scientific knowledge and providing the foundation for tomorrow's
medical therapies. The Institute is home to three major centers: the
Cancer Center, the Del E. Webb Neuroscience and Aging Center, and
the Infectious and Inflammatory Disease Center. Since 1981, the
Institute's Cancer Center has been a member of the National Cancer
Institute's prestigious Cancer Centers program. Discoveries by
Burnham scientists have contributed to the development of new drugs
for Alzheimer's disease, heart disease and several forms of cancer.
Today the Institute employs over 725, including more than 550
scientists. The majority of the Institute's funding derives from
federal sources, but private philanthropic support is essential to
continuing bold and innovative research. For additional information
about the Institute and ways to support the research efforts of the
Institute, visit
http://www.burnham.org
.
