The study, published in the Nov. 13 issue of Nature, for the first time identifies the molecular switches that decide whether the liver stores or burns fat. Knowledge of these switches may provide a new avenue for treating adult-onset diabetes.

Dr. Marc Montminy, professor in the Clayton Foundation Laboratories, and his team discovered the chemical relay that controls whether the body burns sugars or fats for energy. Too much fat released from storage into the bloodstream for burning impedes insulin's ability to promote the uptake of glucose by muscles and other body organs, resulting in insulin resistance and, eventually, diabetes.

While scientists have known how this chemical relay can, in diabetes, provoke the liver to produce too much sugar, they did not know how the body simultaneously produced high levels of fat in the blood. The body tends to then burn fat rather than sugar, making it harder for insulin to deliver sugar to cells. In addition, fats can directly impede insulin uptake by mechanisms that remain unknown.

"Insulin resistance is a predictor of diabetes; like a battery-powered remote control, insulin's ability to process sugars can wear down with repeated use. Eventually, it becomes progressively difficult for insulin to get sugar into muscle and other cells and meet those cells' energy needs," Montminy said. "This study identifies the chemical relays that lead to this state of insulin resistance, which may help us design better treatments for diabetes."

Montminy studied the effects of fasting in mice, which triggers the same hormonal and metabolic responses in the body as human diabetes: increased sugar production and fat burning in the liver. Under fasting conditions, fats, in the form of free fatty acids, enter the blood and end up in the liver, where they can either be stored or burned for en
'"/>

Contact: Andrew Porterfield
porterfield@salk.edu
858-453-4100 x1340
Salk Institute
12-Nov-2003