New research suggests that microbes in the gut may play an important role in how the diabetes drug metformin works. (Image credit: THOM LEACH/SCIENCE PHOTO LIBRARY via Getty Images)
Since the 1990s, metformin has been prescribed to treat type 2 diabetes, but its mechanisms of action have remained unclear to scientists.
A new study offers new insight: Metformin helps move glucose from the bloodstream into the gut, where bacteria process the carbohydrates and create compounds that can help control blood sugar levels.
In a study published March 3 in the journal Communications Medicine, researchers found that metformin treatment increased the amount of glucose released into the gut by nearly fourfold. This appears to promote the production of fatty acids, which help protect the gut and reduce inflammation.
Diversity of paths
Most studies have focused on metformin’s effects on the liver, where it enhances cells’ response to insulin and suppresses glucose synthesis. However, some studies suggest that metformin may also affect the gut, possibly blocking the absorption of glucose into the bloodstream.
“Many researchers are studying the effects of metformin on the gut because the gut is exposed to high concentrations of metformin when taken orally,” said senior study author Dr. Wataru Ogawa, a medical researcher at Kobe University in Japan. (Ogawa has received research support and lecture fees from metformin manufacturer Sumitomo Pharma.)
Ogawa’s team previously demonstrated that the body secretes glucose into a hollow channel in the human intestine known as the lumen, which is where food and waste move. This is seen in people with and without diabetes. “This suggests that this is a physiological function that is inherent in humans,” Ogawa told Live Science.
Nutrition of intestinal microbes
In a new study, scientists found that metformin increased the rate of glucose release into the gut by nearly fourfold in five patients with type 2 diabetes, and these results were confirmed in mice.
Shifting glucose from the circulation to the gut may directly lower blood sugar levels, but the researchers told Live Science that they believe this is only part of metformin's therapeutic effects.
Nicola Morris, a metformin researcher at the University of Dundee in Scotland who was not involved in the study, told Live Science in an email: “I don't expect this to be the drug's primary mechanism of action.”
Other experts noted that in addition to moving sugar out of the bloodstream, the released glucose may also indirectly affect blood sugar levels by feeding gut bacteria.
Dr. Jose-Manuel Fernandez-Real, a medical researcher at the University of Girona in Spain who was also not involved in the study, told Live Science: “Some bacteria, particularly those that use simple sugars, may grow faster, while others that process complex carbohydrates or fiber may be less affected.”
A glucose molecule is made up of six carbon atoms, so to determine how quickly gut bacteria break down glucose, Ogawa had to find a way to track those carbon atoms. His team injected mice with glucose laced with a “heavy” isotope, a version of carbon with an extra neutron. This allowed them to track the heavy carbon atoms as the bacteria converted the glucose into other compounds.
Stool samples showed that bacteria in the metformin-treated mice converted heavy glucose into short-chain fatty acids (SCFA). “Bacteria that produce SCFAs tend to be ‘good’ microbes,” suggesting that metformin’s effects may promote a healthy microbiome, Ogawa noted.
Treatment
Sourse: www.livescience.com
