Researchers reduce blood glucose production as a treatment for diabetes

Researchers have figured out how to lower blood glucose levels by reducing the production of glucose in the liver. They accomplished this in a mouse model by removing a liver protein involved in glucose production, according to a study published online September 3, 2015 in Cell Metabolism. This discovery is already being investigated as a potential treatment for people with diabetes.

“We think this strategy could lead to more effective drugs for type 2 diabetes,” said principal investigator Brian N. Finck, PhD, associate professor of medicine in the Division of Geriatrics and Nutritional Science at Washington University School of Medicine, in St. Louis, MO. “A drug that shuts down glucose production has the potential to help millions of people affected by the most common form of diabetes.”

The research team, led by first author Kyle S. McCommis, PhD, a postdoctoral research scholar at Washington University School of Medicine, focused on the transportation of pyruvate across the inner mitochondrial membrane in liver cells. Transporting pyruvate into the mitochondria is important for normal gluconeogenesis, but in people with diabetes it contributes to hyperglycemia.

To determine the extent of pyruvate’s importance in diabetes, the investigators bred mice that lacked mitochondrial pyruvate carrier 2 (MPC2), the liver-specific mechanism of transporting pyruvate. They found that deleting MPC2 in mice impaired, but not completely abolished, glucose production in the liver. They speculated that alterations in amino acid metabolism might be making up for the loss of MPC2. Indeed, when they proceeded to test this in mice, they found it further reduced mitochondrial pyruvate metabolism and glucose production.

Previous research had suggested that interfering with pyruvate may limit glucose production in the liver, the researchers noted, but this study is the first to demonstrate the critical role played by the pyruvate transport protein.

This research has already resulted in the creation of the drug compound MSDC-0602, an oral medication now in clinical trials as a treatment for type 2 diabetes.