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The brain may offer a target for treating type 2 diabetes

Injection of growth factor into rodent brains normalizes blood glucose levels for four months

by Michael Torrice
May 26, 2016 | A version of this story appeared in Volume 94, Issue 22

Credit: Shutterstock
About 6 million people in the U.S. use insulin to maintain healthy blood glucose levels, according to the Centers for Disease Control & Prevention.
A man injects insulin into his stomach.
Credit: Shutterstock
About 6 million people in the U.S. use insulin to maintain healthy blood glucose levels, according to the Centers for Disease Control & Prevention.

Some patients with diabetes inject themselves with insulin multiple times each day to keep their blood sugar at healthy levels.

Researchers now report that a single injection of a protein called fibroblast growth factor 1 (FGF1) into the brains of diabetic rodents normalizes the animals’ blood glucose levels for at least 18 weeks (Nat. Med. 2016, DOI: 10.1038/nm.4101).

The findings, the scientists say, suggest the brain plays a role in regulating how the liver and muscle handle glucose, and they point to the brain as a possible target for a diabetes therapy with sustained effects.

Previous studies have shown that FGF1 plays a role in metabolism. Levels of FGF1 in the blood “go up when you eat and go down when you’re starving,” says Ronald Evans of the Salk Institute for Biological Studies, who was not involved in the new work.

In 2014, Evans and colleagues showed that injecting FGF1 into diabetic mice—though not into their brains—restored healthy blood glucose levels for about two days.

Michael W. Schwartz of the University of Washington and colleagues wondered if the protein was acting, in part, through circuits in the brain. There are receptors for FGF proteins in the hypothalamus, a part of the brain known to regulate hunger and metabolism, says Washington’s Jarrad M. Scarlett, the new study’s lead author.

To find out, the team injected the protein into the brains of rats and mice with type 2 diabetes.

Although the exact mechanism is unknown, FGF1 in the brain increases the uptake of glucose by the liver and muscle. But this FGF1 mechanism doesn’t seem to cause hypoglycemia—a condition in which glucose levels drop too low. Diabetic patients have to worry about hypoglycemia when they use insulin because the hormone can push glucose levels below a healthy range.

Evans says these results and those from his lab point to a previously unknown mechanism involved in blood glucose regulation that could be exploited for new diabetes therapies.

In addition to further studying FGF1’s actions in the brain, Scarlett says, his team is also looking into ways to deliver FGF1 in patients without invasive brain injections. One possibility could be a nasal spray containing the protein.



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