A new study, published online in Nature, has found that metformin, which is a drug used to treat diabetes, works differently than scientists had previously understood. The team of researchers found that, in mice, metformin suppresses glucagon’s ability to generate an important signalling molecule.
Glucagon is a hormone in your liver, and this discovery is important to the wellbeing of diabetics, as the discovery about how it is affected could point to new drug treatments. In the last fifty years, biguanides, such as metformin, have been one of the few classes of therapeutics that have effectively reduced the overactive glucose production associated with diabetes. The wellness of people with type 2 diabetes, and other insulin-resistant diseases, is greatly affected by insulin’s inability to keep liver glucose output in check, as it leads to high blood sugar.
The study was led by senior author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Medicine, with the Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, who explained ‘Overall, metformin lowers blood glucose by decreasing liver production of glucose, but we didn’t really know how the drug accomplished that.’
Though metformin is a successful drug, not knowing how it works is still a problem. As many people are resistant to metformin, knowing how it works could point to the reason why, and a way to fix this. Also, metformin does come with several adverse side effects. The team knew that when you don’t take in food and your glucose decreases, your pancreas secretes glucagon to signal your liver to produce glucose, so they wondered if metformin works by stopping the glucagon cascade.
The results were that metformin antagonizes the action of glucagon, which reduces your fasting glucose levels. The team also found that metformin leads mice accumulating AMP, which inhibits an enzyme called adenylate cyclase, and eventually blocks glucagon-dependent glucose output from your liver cells. Therefore, the team predict that adenylate cyclase could potentially be the next drug target, which could reduce the adverse side effects that people who take metformin experience, and even work for those patients who are resistant to metformin.
Comments are closed.