Targeting glucagon action: A new frontier for regulating diabetes

For the first time, scientists at the Toronto General Research Institute showed that targeting glucagon action in the brain may be a new frontier for regulating diabetes.

An international team led by Senior Scientist Dr. Tony Lam showed how glucagon regulates the hypothalamus' control over blood sugar.

In experimental models of obesity and diabetes, researchers determined that resistance to glucagon in the brain leads to increases in blood sugar levels, a trait of these conditions. However, direct stimulation of the protein kinase A signaling pathways (PKA) in the brain bypasses the resistance and decreases blood sugar levels.

The study, entitled "Hypothalamic glucagon signaling inhibits hepatic glucose production" was published today in the on-line edition of the international journal, Nature Medicine. It paves the way for investigation of a potentially new way of decreasing blood sugar levels in diabetes and obesity, by increasing glucagon action in the brain.

Glucagon is a hormone secreted by the pancreatic islet α-cells when blood sugar levels fall too low. It is known that glucagon functions in the liver to cause blood sugar levels to increase. However, this increase is temporary and blood sugar levels return to normal. This decrease in blood sugar is thought to occur through glucagon action in the hypothalamus.

In diabetes, glucagon's transient increase in blood sugar is impaired and levels remain elevated. Currently, insulin is the most common means of regulating blood sugar levels in diabetics.

"Studying glucagon action in the in the brain is a totally new area of investigation for potential treatment of diabetes. Drugs that aim to increase glucagon action in the brain and/or block glucagon action in the liver could regulate sugar levels in diabetes," said Dr. Tony Lam, who holds the J.K.McIvor (1915-1942) Endowed Chair in Diabetes Research and Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto. Dr. Lam is also Associate Professor, Departments of Medicine and Physiology, University of Toronto, Associate Director, University of Toronto Banting and Best Diabetes Centre and Senior Scientist at the Toronto General Research Institute.
"I believe that down the road, treating diabetes with glucagon therapy will be equally as effective as insulin therapy," Dr. Lam added.