Contact: Alison Heather
Diabetes treatment may lie in helping muscles to burn fat better
28 January 2009 -- Scientists in
Sydney and Melbourne have produced results that could silence the
current debate about exactly how fat molecules clog up muscle cells,
making them less responsive to insulin.
The finding is an
important milestone in understanding the mechanisms of obesity related
insulin resistance, a precursor of Type 2 diabetes.
Bruce, first working with Professor Ted Kraegen from Sydney's Garvan
Institute of Medical Research, and then with Professor Mark Febbraio
from Melbourne's Baker IDI Heart and Diabetes Institute, has added to
evidence that fat molecules clog up the cytosol, or cell interior, but
not the mitochondrion, or energy powerhouse of the cell.
is an important distinction because the groups have also found a way to
reduce the build-up of fat molecules in the cytosol by increasing the
ability of mitochondria to take in fat molecules and burn them.
finding, already online and critical for our understanding of fat
metabolism, will be published in a future issue of the prestigious
believes the finding indicates a direction for further pre-clinical
research. "There's a lot of work being put into developing new drugs
and methodologies for improving insulin action," he said.
work clarifies what are likely to be the important therapeutic
directions to improve insulin action in muscle and hence new approaches
for the treatment of Type 2 diabetes."
Kraegen and colleagues
made one small change to a single muscle in one leg of a rat, allowing
that muscle to burn fat molecules better. To do this, they
overexpressed a protein (CPT1) that acts like a "gate" or "tap" to
control entry of fat molecules into mitochondria.
changed muscle burned more fat molecules and became significantly more
responsive to insulin than the equivalent muscle in the opposite leg,
which had not been re-engineered.
While this result is very
promising, it also sets up a conundrum, which Professors Kraegen and
his colleagues at Garvan are examining in their next phase of research.
The problem they face is that a muscle uses a certain amount
of energy depending on the work it is doing. If it gets that energy by
burning more fats, it will require less glucose, creating an imbalance
of another kind.
"So what we're trying to do is mimic exercise with pharmacological agents," explained Kraegen.
examining agents that make the muscle burn more fuel to get the same
amount of energy. In other words, we're trying to make energy
conversion less efficient."
"If we succeed in producing this effect, it will make our current finding very potent indeed."
The Garvan Institute of Medical Research was founded in 1963.
Initially a research department of St Vincent's Hospital in Sydney, it
is now one of Australia's largest medical research institutions with
nearly 500 scientists, students and support staff. Garvan's main
research programs are: Cancer, Diabetes & Obesity, Immunology and
Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The
Garvan's mission is to make significant contributions to medical
science that will change the directions of science and medicine and
have major impacts on human health. The outcome of Garvan's discoveries
is the development of better methods of diagnosis, treatment, and
ultimately, prevention of disease.
All media enquiries should be directed to:
Alison Heather 0434 071 326