In mice with diet-induced diabetes—the equivalent of type 2 diabetes in humans—a single injection of the protein FGF1 is enough to restore blood sugar levels to a healthy range for more than two days. The discovery by Salk scientists, published today in the journal Nature, could lead to a new generation of safer, more effective diabetes drugs.
The team found that sustained treatment with the protein doesn't merely keep blood sugar under control, but also reverses insulin insensitivity, the underlying physiological cause of diabetes. Equally exciting, the newly developed treatment doesn't result in side effects common to most current diabetes treatments.
Controlling glucose is a dominant problem in our society," says Ronald M. Evans, director of Salk's Gene Expression Laboratory and corresponding author of the paper. "And FGF1 offers a new method to control glucose in a powerful and unexpected way."
Type 2 diabetes, which can be brought on by excess weight and inactivity, has skyrocketed over the past few decades in the United States and around the world. Almost 30 million Americans are estimated to have the disease, where glucose builds up in the bloodstream because not enough sugar-carting insulin is produced or because cells have become insulin-resistant, ignoring signals to absorb sugar. As a chronic disease, diabetes can cause serious health problems and has no specific cure. Rather it is managed—with varying levels of success—through a combination of diet, exercise and pharmaceuticals.
In 2012, Evans and his colleagues discovered that a long-ignored growth factor had a hidden function: it helps the body respond to insulin. Unexpectedly, mice lacking the growth factor, called FGF1, quickly develop diabetes when placed on a high-fat diet, a finding suggesting that FGF1 played a key role in managing blood glucose levels. This led the researchers to wonder whether providing extra FGF1 to diabetic mice could affect symptoms of the disease.
Evans' team injected doses of FGF1 into obese mice with diabetes to assess the protein's potential impact on metabolism. Researchers were stunned by what happened: they found that with a single dose, blood sugar levels quickly dropped to normal levels in all the diabetic mice.
"Many previous studies that injected FGF1 showed no effect on healthy mice," says Michael Downes, a senior staff scientist and co-corresponding author of the new work. "However, when we injected it into a diabetic mouse, we saw a dramatic improvement in glucose."