Diabetes results from a lack of functioning insulin, a hormone that stimulates cells to take up glucose (a type of sugar) from the bloodstream. Cells need glucose as fuel to produce energy. Type 1 diabetics lack insulin because their immune systems destroy the pancreatic cells that produce it. In type 2 diabetics, cells no longer respond properly to insulin. Either way, without sugar that can be converted to energy, cells starve and glucose levels build up in the blood, which can lead to life-threatening complications such as heart disease.

“When mice – or people – eat too much fat, they become obese and increasingly resistant to insulin, an early sign of type 2 diabetes,” explained Dr. Julio Ayala, assistant professor at Sanford-Burnham’s Lake Nona campus.

Given their roles in diabetes, it stands to reason that insulin and glucose metabolism must be carefully regulated in order to keep the body running smoothly. One way our bodies do this is by producing a hormone called glucagon-like peptide 1 (Glp1) after we eat. The gut secretes Glp1, which travels through the bloodstream and is received by receptors in the pancreas.  This boosts production of insulin, thus telling cells to take up more glucose from the blood.

Dr. Ayala believes that Glp1 does more than just stimulate the pancreas to produce insulin. He studies how this gut hormone also affects glucose metabolism in the liver and glucose uptake by muscle cells. He and his colleagues at Vanderbilt University and Mt. Sinai Hospital in Toronto published a study earlier this month in the journal Endocrinology that provides further evidence that the Glp1 receptor regulates not only the production of insulin, but also how well it works.

If normal mice are fed a high-fat diet, their muscle and liver cells eventually become resistant to insulin. In this study, the researchers wondered what would happen if mice engineered to lack the Glp-1 receptor were fed a diet high in fat. They found that disrupting the Glp1 receptor was actually beneficial. When compared to normal mice on a high-fat diet, mice missing the hormone receptor were better at taking up glucose in muscle cells and insulin resistance at the liver was reduced.  This was accompanied by a decrease in fat accumulation in the muscle and liver – hallmarks of insulin resistance.

“We hypothesized that disrupting Glp1 signaling in mice on a high fat diet would be a double whammy – we thought they would experience both increased fat accumulation and impaired insulin action at the liver,” Dr. Ayala said. “But to our surprise, we got the completely opposite result. These mice actually have improved insulin action at the liver.”

This study proposes a new role for the Glp1 receptor in regulating the balance between fat and glucose metabolism, making it an attractive target for new diabetes therapies.