In a new study entitled “Loss of mitochondrial pyruvate carrier 2 in liver leads to defects in gluconeogenesis and compensation via pyruvate-alanine cycling,” scientists discovered a key protein in livers mitochondria – mitochondrial pyruvate carrier 2 (MPC2) – that controls glucose synthesis and is a potential target for new diabetes therapies. The study was published in the journal Cell Metabolism.
Type 2 diabetes occurs when a patient’s pancreas starts producing less insulin and/or the tissues within the body fail to respond to insulin (a condition referred to as insulin resistance). As such, treatments for type 2 diabetes often work by increasing our body response to insulin, the hormone that allows cells to “take up” sugar (glucose) from the blood and use it as energy.
In this new study, researchers developed a new treatment to counteract type 2 diabetes by focusing on a different mechanism: instead of targeting insulin with the objective of decreasing high glucose levels, scientists at Washington University School of Medicine, St. Louis devised a new strategy that decreases the production of glucose in the liver.
The biosynthesis of new glucose (known as gluconeogenesis), a critical process that is switched on in order to maintain normal glucose levels in the blood during periods of food deprivation, takes place in the liver. This process, however, contributes to high glucose levels in the blood whenever a patient has a condition of insulin deficiency or resistance.
The research team used mice and investigated the specific role of a protein – the MPC2 – in the liver and how it contributes to gluconeogenesis. They discovered that deleting this protein in mouse livers impaired gluconeogenesis and protected mice from hyperglycemia (high blood glucose). The MPC2 protein works by transporting from the blood to liver cells a key element for the synthesis of new glucose, pyruvate, specifically to the cells’ factories, the mitochondria.
The team worked closely with researchers at the University of Texas Southwestern Medical Centre and the biopharmaceutical Metabolic Solutions Development Co, testing a new drug called MSDC-0602 developed by the company and currently in clinical trials for type 2 diabetes. This drug targets selectively mitochondria metabolism and they showed that it was efficient at suppressing hepatocyte glucose production potentially by interacting with the protein MPC.
Brian N. Finck, PhD, associate professor of medicine in the Division of Geriatrics and Nutritional Science and study lead author commented on the findings and its impact on diabetes treatments, “We think this strategy could lead to more effective drugs for type 2 diabetes. A drug that shuts down glucose production has the potential to help millions of people affected by the most common form of diabetes.”