Gut plays a key role for diabetes drug, researchers discover – and that could mean better treatment

Until now, scientists always assumed Metformin, the world’s most common type 2 diabetes treatment, worked directly on the liver. But U of T researchers found it acts first on the gut.

They found the same results when testing resveratrol, the compound found in red wine. 

Tony Lam, a professor of physiology and medicine, and his team showed that the gut is responsible for sensing both Metformin and resveratrol and then signalling the brain to reduce glucose production in the liver.  Uncovering the gut’s crucial role in diabetes treatment could help scientists design medications that focus on the gut, rather than the liver – a major advantage. 

“We already knew that the brain and liver regulate blood glucose levels, but how do you target either of these two organs without side effects?” said Lam, who holds the Canada Research Chair in Obesity and John Kitson McIvor Endowed Chair in Diabetes Research and is associate director of research at U of T’s Banting and Best Diabetes Centre and senior scientist at the Toronto General Hospital Research Institute. 

“We may have found a way around this problem by suggesting the small intestine can be the initial target instead,”  Lam said, adding that the gut is accustomed to dealing with new substances, and adapts to treatment better than the brain or liver, leading to fewer side effects. 

It’s significant that Lam found the same results with both Metformin and resveratrol. The substances are different from each other, but both triggered molecules in the gut that helped lower blood glucose. This adds to the evidence for developing new treatments focused specifically on the gut. 

Lam emphasized that it will take a number of years of experimental work to determine whether the current findings, which were discovered in rodents, are relevant in humans.

Two related studies were published back-to-back online in Nature Medicine on April 6, 2015. (Read about metformin and lower hepatic glucose production in rats; read about resveratrol reversing insulin resistance in rats.)

Read more about U of T research related to diabetes, including:

• diabetes and exercise
• diabetes and diet
• diabetes and dairy
• diabetes and pregnancy
• diabetes and geography
• diabetes and drug therapies 

Read about a U of T startup working on diabetes management.

Heid Singer is a writer with the Faculty of Medicine at the University of Toronto.