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.
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.
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."