‘The Swiss Army knife of metabolism’: studying the uses of gut hormones around the body 2 February 2022 Recent studies at the University of Toronto’s Termerty Faculty of Medicine have shown how gut hormones that help control insulin and blood glucose levels could also prove helpful in other areas of the body. These hormones, known as glucagon-like peptides (GLP-1 and GLP-2), were discovered some years ago by a group of researchers that included Professor Daniel Drucker, who has led the most recent studies. GLP-1 and GLP-2 are naturally occurring hormones within the body that stimulate the production of insulin, regulate blood glucose, and appear to aid weight loss by slowing digestion. In people with type 2 diabetes, these hormones are often produced at much lower levels, and are administered through medication known as GLP-1 agonists, that mimic the work of the hormone. After having a hand in the research that created these life-changing medicines for people with diabetes, Drucker has turned to examining how these hormones might assist with other metabolic conditions such as liver disease, as well as cardiovascular conditions and Alzheimer’s disease. A key asset of the GLP-1 hormone is its anti-inflammatory properties. As many conditions in the body spring from inflammation, harnessing this power could prove useful in a multitude of ways. The only problem? Researchers are not still quite sure how it works. In an effort to learn more about this hormone, Drucker’s research team studied how GLP-1 receptors within mouse immune cells reacted with GLP-1 drugs to reduce plaque within the arteries, and fat and inflammation within the liver. The results showed that the GLP-1 receptors played an important role in the medicine’s efficiency. Drucker said it was exciting to identify these receptors in specific immune cells, and how they might be necessary to get the full benefits of GLP-1 medication. ‘This paper is the first to show that …the animals that were missing the GLP-1 receptor in the immune cells in the liver did not have the same therapeutic benefit,’ Drucker says. Though this study pushes researchers one step closer to understanding how GLP-1 interacts with the body, there are still many more questions to be answered. ‘If I could figure out how GLP-1 reduces heart attacks and strokes, and I knew where that magic was happening, maybe we could make even better, more targeted GLP-1 therapies to produce more effective medicines,’ he said. ‘There’s a huge amount of uncertainty as to how GLP-1 controls inflammation in different organs in the body, and that’s a major focus for our lab right now.’ This uncertainty does not stop Drucker from expressing excitement about the potential of the GLP-1 hormone. ‘Whether it’s in the pancreas, blood vessels, the liver, or the brain, increased inflammation is a driving component of the pathology of all kinds of different diseases,’ he says. ‘I believe that one reason GLP-1 is the Swiss Army knife of metabolism – that it can do so many different things in so many different organs – is its ability to reduce inflammation.’ Already a game-changer in the lives of people living with type 2 diabetes, this new research is the beginning of a journey to discover how this power-packed hormone might further benefit the body. Key points Researchers are continuing to discover the roles and benefits of the GLP-1 gut hormone GLP-1 agonist medications already assist people with type 2 diabetes immensely, as the hormone can help balance blood glucose levels and stimulate insulin production. Once it is understood more, the anti-inflammatory properties of GLP-1 could be used in other parts of the body, such as the liver and the heart. You can read the full study here.