Ronald Evans, PhD, from the Salk Institute for Biological Studies, will receive $1.2 million over four years as part of a Network Grant from the Larry L. Hillblom Foundation to examine a molecular pathway that regulates blood sugar and fat independent of insulin. The research is expected to advance understanding of type 2 diabetes and could lead to the development of new therapies for treating the disease.
Evans is professor and director of the gene expression laboratory. He also serves as the March of Dimes chair in molecular and developmental biology. Other members of his team include Jin Zhang, PhD, and Alan Saltiel, PhD, both professors from the University of California, San Diego.
“We are very thankful to the Larry L. Hillblom Foundation for funding Ron’s project about this molecular pathway that could be targeted to treat type 2 diabetes,” said Rusty Gage, PhD, professor and president of Salk. “This work represents an exciting new avenue of diabetes research with many possibilities for translation into the clinic.”
Recently, the Evans lab discovered that a hormone called FGF1 regulates glucose by inhibiting lipolysis, and thus simultaneously lowers both blood glucose and fat. This effect is rapid and similar to how insulin works. While insulin acts through a regulatory switch called PDE3, Evans found that FGF1 uses a parallel pathway called PDE4. This finding is important as insulin action is greatly reduced in people with type 2 diabetes.
The Evans study further shows that even when insulin action is blocked, FGF1 continues to control both lipolysis and blood glucose levels. Insulin resistance is considered to be a major problem and hard to control, so FGF1 represents a novel target for developing therapies for type 2 diabetes. Now, with funding from the Larry L. Hillblom Foundation, the group will examine the FGF1 pathway in more detail, explore where the pathway is located in the cell, and test how the pathway functions during different forms of diabetes.
“Understanding this glucose-regulating mechanism will provide fundamental insight into how blood glucose is maintained and could lead to the development of new treatments for diabetes,” said Evans.