Jul 2, 2018
The drug metformin has
been used to control blood sugar in many patients with Type 2 diabetes for more
than two decades. Now scientists at the University of Alabama, Birmingham, have
amassed evidence that the drug’s ability to target cell metabolism could help
repair the lung.
The team is investigating
therapies for pulmonary fibrosis, a condition that can occur after lung injuries
from infections or treatments like chemotherapy. They are particularly
interested in finding effective treatments for idiopathic pulmonary fibrosis
(IPF), a progressive, fatal disease that can strike out of the blue and affects
more than 5 million patients worldwide.
The scientists zeroed in
on cells called myofibroblasts, which are responsible for depositing the
damaging collagen that proliferates in lung fibrosis. They found that the activity of an enzyme
called AMP-activated protein kinase (AMPK) was suppressed in fibrotic areas of
tissue samples taken from IPF patients. The metabolisms of those cells went
into overdrive, making them less likely to undergo apoptosis, or programmed
cell death.
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Metformin activates AMPK.
In experiments with the tissue samples and lung fibroblasts from mice, the
researchers found that metformin reversed lung fibrosis. So they decided to try
the diabetes drug in mouse models of lung fibrosis. They started the treatment
three weeks after the lungs were damaged—making the lung fibrosis well
established—and continued it for the next 5 weeks. That accelerated lung
repair.
To confirm their
suspicion that AMPK was the key to metformin’s activity in myofibroblasts, they
tried the same experiment in mice that lacked the enzyme. Lung fibrosis did not
improve in those animals. They published their research in the journal Nature
Medicine.
Metformin has long been
of interest in the oncology community because observational studies have shown
that diabetics who take the drug have a lower risk of cancer than those who
don’t. The drug's effect on AMPK seems to play a role there. Scientists at
the University of California, San Diego, discovered that metformin activates a
protein pathway that prompts AMPK to build barriers in the body against inflammation
and other cancer-causing stressors, for example.
Scientists are also
studying the potential of metformin in treating other conditions,
including autism and disorders of aging like heart disease.
The University of Alabama
researchers believe their study shows that AMPK is a “critical metabolic
switch” that shifts the metabolism of lung cells so they can resolve fibrosis,
they wrote in their study. "Additionally, we provide proof-of-concept that
activation of AMPK by metformin or other pharmacologic agents that activate
these pro-resolution pathways may be a useful therapeutic strategy for
progressive fibrotic disorders."
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