Familiar protein restores insulin sensitivity
Ron Evans in his Lab at Salk Institute
July 17, 2014
Ron Evans is a Salk Institute scientist who led a major research study about a potential new diabetes therapy. Evans, has found that a well-known protein could provide a powerful new therapy for Type 2 diabetes. The protein resensitizes patients to insulin who have developed insulin resistance.
A new way to restore insulin sensitivity has been demonstrated in diabetic model mice by a team led by Salk Institute researchers. Testing of this approach in people should be straightforward, said principal investigator Ron Evans.
Subcutaneous injections of a well-known protein called FGF1, for fibroblast growth factor-1, brought down blood glucose levels to normal in the mice. It did not cause hypoglycemia. Moreover, the protein did not produce side effects of other insulin-sensitizing drugs, such as weight gain, bone loss and the buildup of liver fat.
The research was published Wednesday in the journal Nature. Evan and Michael Downes are senior authors; Jae Myoung Suh is the first author.
FGF1 and insulin sensitivity
Type 2 diabetes is characterized by resistance to insulin, so more of the hormone is needed to bring down blood glucose. How the process occurs isn’t clear. The disease is associated with obesity, cardiovascular disease, glaucoma and nerve damage.
FGF1 has been known for decades, and used to stimulate local tissue repair, said Daniel Einhorn, a Scripps Health endocrinologist and friend of Evans. But its role in glucose regulation had not previously been suspected. Injections of FGF1 into normal mice did nothing.
Evans said his team discovered genetic clues that FGF1 was inactive in Type 2 diabetes, and decided to put that to the test. FGF1 doesn’t normally circulate, acting intracellularly. Injecting the protein caused it to act like an endocrine hormone. Evans’ team described that process as “endocrinization”.
Evans said other insulin-sensitizing compounds usually affect many genes, which explains the side effects.
“You have to balance the benefit against the adverse complications,” Evans said. “We have an advantage with our particular discovery that working with FGF1, you’re just dealing with one thing.”
Diabetes specialist Matthias von Herrath agreed that the study is significant, adding that more studies are needed to ensure that the results apply to people.
“The study by Evans and colleagues found that both in vitro and in vivo there were anti-inflammatory and insulin metabolism (sensitivity) improvements . . .. ” von Herrath, a professor at the La Jolla Institute for Allergy & Immunology, said by email. “Future studies will need to make sure that these interesting findings in animals in vitro and in vivo will have correlates that are likely to translate to in vivo understanding in humans.” Von Herrath is also a vice president at NovoNordisk.