In many patients with type 2 diabetes, the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. Scientists at the Salk Institute for Biological Studies discovered a key cellular switch that controls glucose production in liver cells.
This switch may be a potential new target for the development of highly specific diabetes drugs that signal the liver to reduce the production of sugar. The Salk researchers, led by Marc Montminy, a professor in the Clayton Foundation Laboratories for Peptide Biology, published their findings in the Sept. 7th online issue of Nature.
"It is very exciting to understand how glucose production in the liver is regulated. Now, we can try to improve the way how type 2 diabetics handle blood sugar," says Montminy.
The newly discovered switch, a protein named TORC2, turns on the expression of genes necessary for glucose production in liver cells.
When describing glucose's role in health and disease, Montminy compares the human body to a hybrid car that runs on a mix of fuels depending on its activity status: gas, or glucose, is used for high-energy activities, and battery power, or body fat, for low-energy activities. During the day, when food refuels the "gas tank," the body burns mainly glucose, and during sleep, it burns primarily fat.
The body switches from glucose to fat burning mainly in response to two key hormones -- insulin and glucagon -- that are produced by the pancreas. During feeding, the pancreas releases insulin, which promotes the burning of glucose. At night, however, the pancreas releases glucagon into the bloodstream, which signals the body to fire up the fat burner.
But even during sleep, our brain needs a constant supply of glucose to function properly. For that reason, our body actually manufactures glucose during sleep or when we are fasting. That process, called gluconeogenesis, is carried out mainly in the liver.
Insulin normally shuts down the ability of the liver to produce glucose. In individuals with Type II diabetes, however, insulin is unable to inhibit sugar production in the liver, "either because the pancreas is not producing enough insulin or because insulin's signal can't be 'heard,'" says Montminy. When the liver is unable to hear the insulin signal, excess glucose builds up in the bloodstream.