Targeting Brain Signaling Can Reduce Blood Glucose in Diabetic Mice
An animal study found that injecting a hormone directly into the brain of rodents put type 2 diabetes in remission for several months. Though the authors suggested that the finding could lead to a treatment for diabetes, they also cautioned that the hormone could also have unwanted side effects in the brain and much more research is needed.
Prior research1 had found that fibroblast growth factors (FGF), a group of hormones, help regulate glucose metabolism among other functions. One group of researchers found that when rodents were given high doses of FGF1 in the body (not the brain), it lowered blood glucose for up to 48 hours.
“We thought that FGF1 could be acting in the brain, because the receptors for FGF1 are highly prevalent there,” says the study’s lead researcher Jarrad Scarlett MD, PhD, a scientist at the Seattle Children’s Hospital, University of Washington. That led them to look at what would happen if the hormone was injected directly into the brain of mice or rats with type 2 diabetes.
Their study, published online this week2 in Nature Medicine, found that a single injection or FGF1 normalized the animals’ blood glucose levels for at least the next four months.
Dr. Scarlett believes that the hormone targets brain circuits involved in regulating blood glucose levels. “We think that diabetes represents a dysfunction of neural circuits within the brain,” he says.” What FGF1 is doing is acting upon these circuits to ameliorate the dysfunction.” These particular neural circuits regulate peripheral tissues, specifically how much glucose they take up, and how fast they metabolize it, he says.
Though the researchers were not surprised that the hormone lowered glucose levels, they were surprised at how long the effect lasted after a single injection. “We were expecting the results to last 48 to 72 hours, not several months,” says Dr. Scarlett. “We think it’s stimulating synaptic remodeling within these circuits,” he says.
The researchers controlled for changes in food intake or body weight, which indicates that the improvement in blood sugar levels were not related to weight loss.
“From a bigger picture standpoint, the study shows that the brain does have the ability to promote long-lasting glucose lowering,” says Dr. Scarlett. Whether FGF1 will be the best therapeutic compound remains to be seen. The hormone also has mitogenic effects--causing cells to grow and divide—which could make it carcinogenic.
The goal is to somehow reduce the mitogenic effects of FGF1 or look for other compounds that have similar effects without the mitogenic effects.