Scientists discover new understanding of how an ancient hormone works, paving the way for better therapies

Monash University researchers have discovered how the peptide hormone glucagon could better treat diseases such as obesity and type 2 diabetes, which affect billions of people.

Glucagon, like insulin, originating from the pancreas, has been known for 100 years, but its functioning is only beginning to be understood. An international team led by the Monash Biomedicine Discovery Institute has discovered potential new ways to make better medicines using preclinical models and cellular experiments combined with viral/molecular technologies.

The results are now published in Natural communicationsrevealing how glucagon sends signals in cells and the liver and, for the first time, defines how tiny cell membranes move proteins – the vesicle trafficking protein SEC22B.

Lead author Associate Professor Adam Rose, Director of the Monash Nutrient Metabolism and Signaling Laboratory at the Biomedicine Discovery Institute, said: “By creating a clearer understanding of how glucagon works, we can potentially create more effective therapies. refined and better for diseases such as obesity and type 2 diabetes. This can have positive economic and societal implications, but, more importantly, it can improve the lives of people with metabolic disease.

Associate Professor Rose said that despite glucagon being discovered more than 100 years ago, how it works in the liver was still largely unknown. Glucagon is secreted by certain cells in the pancreas to increase glucose levels in the blood and liver, making it part of the puzzle of type 2 diabetes, keeping blood sugar high, while insulin keeps it high. keeps it at a low level. The two work together to stabilize blood sugar levels, but glucagon also affects many other aspects of metabolism.

“Glucagon is a hormone that has been known for a relatively long time, but we did not yet know how glucagon signals in the liver for its many effects,” Associate Professor Rose said. “Our findings change that by uncovering a host of new possibilities.”

He said glucagon drugs are becoming best-in-class for treating obesity, type 2 diabetes and fatty liver disease. “Our studies pave the way to discovering how these therapies actually work. We examined one such possibility and showed for the first time that a vesicular trafficking protein is involved in almost all of glucagon’s metabolic actions.”

Associate Professor Rose said the next step towards better drugs for type 2 and obesity was to better understand the vesicle trafficking protein SEC22B and how it works in a liver cell to affect glucagon action.