A recent study published in the journal Cell Metabolism revealed that the gut immune system plays an important role in the development of diabetes. The study, which was led by researchers at the Toronto General Research Institute (TGRI) at the University of Toronto in Canada and the Stanford University School of Medicine in California, is entitled “Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents.”
Obesity, especially around the waistline or abdomen, is known to increase the likelihood of developing type 2 diabetes. The link between obesity and insulin resistance, which is a major trigger for type 2 diabetes, is not fully understood, but previous studies have shown that immune cells inside abdominal fat induce the release of pro-inflammatory chemicals that make the body less sensitive to insulin, the hormone that controls the levels of blood sugar. Recent studies have also suggested that the bowel also suffers changes in obese individuals, for instance in the gastrointestinal flora, and that these changes can affect inflammation and insulin resistance.
Mesalamine (5-ASA) is an anti-inflammatory agent commonly prescribed for inflammatory bowel disease (IBD), a disorder characterized by increased intestinal inflammation and altered permeability. The research team hypothesized that 5-ASA medication could have a therapeutic effect in insulin resistance associated to obesity and linked to the alterations in the bowel.
To test their hypothesis, researchers analyzed mice that were fed a high-fat, high-calorie diet. They found that these animals had a higher amount of pro-inflammatory immune cells and less regulatory cells of the immune response in comparison to normal mice. These results were corroborated by a similar experiment conducted in obese and healthy humans. The team found that a high-fat diet leads to inflammatory alterations in the bowel’s immune cells, which triggers a chemical cascade that damages the bowel wall, allowing the leakage of bacterial products into the bloodstream. This leakage is responsible for the development of insulin resistance, where cells are unable or less effective in using and respond to insulin in order to stabilize blood sugar levels.
When researchers used the 5-ASA drug to treat bowel inflammation in the obese mice, they found that the drug was able to reverse insulin resistance and bowel inflammation, and lower blood sugar levels to normal values. “By using this drug, we found that we could prevent type 2 diabetes in mice,” said one of the study’s senior authors Dr. Daniel Winer at TGRI in a news release. “If this works in humans, it could change the whole field of diabetes prevention and treatment.”
The research team concluded that the gut immune system is an important modulator of insulin resistance, and that targeting gut inflammation could be a therapeutic strategy against insulin resistance and consequently diabetes in humans. “These results are novel and important because we have identified the immune system that lives in the gut as a new player in the control of blood sugar,” said Dr. Daniel Winer.
“If we could block the pro-inflammatory immune cells at the very beginning of this process, we could treat the disease more effectively,” added one of the study’s senior authors, Dr. Shawn Winer. “By refocusing on the bowel, we open up many more therapeutic options as we already have a number of approved drugs available to treat an inflamed bowel.”
