You’ve probably heard that breakfast is the most important meal of the day. Vanderbilt researchers have discovered why that adage holds weight—especially for the one in nine adults worldwide living with diabetes.
Glucose (the simplest form of sugar) is the body’s main source of energy. When everything is working properly, the body regulates glucose—keeping it from spiking or crashing—and stores it until we need it.
What we eat in the morning influences how the body manages glucose the rest of the day. Scientists call this the “second-meal effect,” in which the makeup of the morning meal shapes how we handle meals later on. But how does that actually work—and what role do the hormones that manage blood sugar, specifically insulin and glucagon, play in the liver’s ability to regulate glucose later in the day?
That question is the focus of a new paper published in Frontiers in Endocrinology, where, building on Vanderbilt’s legacy as a global leader in diabetes research, a team from the Department of Molecular Physiology and Biophysics tackled the “how” behind the second-meal effect head-on. The work was spearheaded by recent Ph.D. graduate Hannah Waterman, with Alan Cherrington, Jacquelyn A. Turner and Dr. Dorothy J. Turner Professor of Diabetes Research and senior author Dale Edgerton, a research professor in the department.
Insulin and glucagon work in opposition: Insulin lowers blood sugar, glucagon raises it. After a meal, insulin primes the liver to store glucose, while glucagon prompts it to release glucose back into the blood. Researchers wanted to know whether glucagon, like insulin, leaves a lasting mark on the liver in shaping how it responds to meals eaten hours later.
The answer? Yes. When glucagon levels were elevated in the morning, the liver had a harder time storing glucose at the next meal—even when insulin and blood sugar levels were identical the second time around. Researchers found that instead of storing glucose, the liver continued to release it, a response researchers traced to lower levels of glucokinase, the enzyme that helps the liver capture and store sugar.
The findings point to glucagon as a bigger player in the second-meal effect than once thought—not just insulin’s opposite, but a hormone that also influences glucose regulation long after a meal has ended.
This reframing matters most for people living with diabetes, particularly type 2 diabetes. It may help explain why blood sugar can climb throughout the day even when morning numbers look normal. It also strengthens the case for treatments that target insulin and glucagon together rather than insulin alone—a direction Vanderbilt knows well. Cherrington, whose career has focused on understanding the metabolic processes that govern blood sugar regulation, helped pioneer the research behind the GLP-1 medications now central to treating diabetes and obesity.
What’s next for the team? Pinpointing the molecular mechanisms behind the second-meal effect. While this study showed that morning hormone levels can influence the liver’s response hours later, the gene and protein networks driving that effect remain unclear. Future work will help fill those gaps and reveal how the process breaks down in metabolic disease.
