Effect of glucagon on blood sugar regulation throughout the day revealed

Insulin and glucagon act as antagonists: insulin lowers blood sugar levels by causing tissues to absorb glucose, while glucagon raises them by stimulating the liver to release stored glucose. After a meal, insulin prepares the liver to store glucose, and glucagon prepares it to release it into the bloodstream. For a long time, the main focus was on insulin, but new research shows that glucagon also leaves a lasting mark on liver function.

The team led by Hannah Waterman, Alan Cherrington, and Dale Edgerton studied how morning glucagon levels affect the liver’s ability to manage glucose during the next meal. The key finding is that if the morning glucagon level was elevated, the liver was less effective at storing glucose during the next meal, even with the same insulin and blood sugar levels.

Instead of storing glucose, the liver continued to release it. Experts have linked this to a reduced level of glucokinase — an enzyme that helps the liver absorb and store sugar. It turns out that high morning glucagon reprograms the liver to continue releasing glucose, and this effect persists for several hours.

Thus, glucagon turned out to be a more significant factor in the “second meal effect” than previously thought, as it not only balances insulin in the moment but also shapes the liver’s response to subsequent meals.

These results are particularly relevant for people with diabetes, especially type 2. They may explain why blood glucose levels can rise during the day, even if they were normal in the morning. From a practical standpoint, the findings strengthen the arguments in favor of treatment approaches that take both hormones into account simultaneously, rather than focusing solely on insulin.

Given that Alan Cherington participated in the research that laid the foundation for GLP‑1‑based medications (which help regulate both insulin and glucagon), these data may influence the further development of diabetes and obesity therapy.