In dogs, morning glucagon disrupts later glucose handling

A liver can appear ready for breakfast and still be carrying instructions from it hours later. In a canine study, Vanderbilt researchers found that elevated morning glucagon made the liver release rather than store glucose at a later meal, even when insulin and blood-sugar levels were identical the second time around.

The result puts a second hormone at the center of the “second-meal effect,” the term scientists use for the way a morning meal shapes the body’s response to food later in the day. Insulin lowers blood sugar and primes the liver to store glucose; glucagon raises blood sugar and prompts the liver to release it. The Vanderbilt team found that glucagon’s influence lingered beyond the morning.

The mechanism they identified involves glucokinase, an enzyme that helps the liver capture and store sugar. After elevated morning glucagon, glucokinase levels were lower, and the liver continued releasing glucose instead of switching to storage when the next meal arrived.

The work was led by recent Ph.D. graduate Hannah Waterman, with Alan Cherrington, Jacquelyn A. Turner and senior author Dale Edgerton at Vanderbilt’s Department of Molecular Physiology and Biophysics. Their paper was published in Frontiers in Endocrinology. Cherrington also helped pioneer research behind GLP-1 medicines used to treat diabetes and obesity.

And then what, concretely? The finding could help explain why blood sugar climbs through the day in people with type 2 diabetes even when morning readings look normal. It also supports the logic of treatments aimed at insulin and glucagon together, rather than insulin alone. The limit is clear: these results come from canines, while the gene and protein networks behind the effect still need to be mapped and the process understood in metabolic disease.