As drug developers race in pursuit of new treatments to control the growing diabetes problem, researchers at Albert Einstein College of Medicine of Yeshiva University have new human evidence that the brain has a hand in glucose production. The results could spark discovery and development of new brain-targeting treatments for diabetics, whose bodies lose the ability to control blood sugar levels.
The brain isn't a known player in the blood-sugar control game, which has long been thought to be the domain of the liver, which produces glucose, and the pancreas, which cranks out insulin to keep glucose levels in check. Yet Einstein researchers have been showing that the brain, which needs glucose to function, has glucose-lowering capabilities in the liver, too, via activation of potassium channels in the hypothalamus.
Building on previous results in rodent tests, 10 non-diabetic humans took the glucose-boosting agent diazoxide in the Einstein experiment. The group was able to show that diazoxide was working in the brain. They confirmed that it crossed the blood-brain barrier and the researchers used a potassium channel blocker infused into the brain that appeared to stymie diazoxide's effects.
These results represent a bit of a comeback for the argument that the brain impacts glucose production. Researchers at Vanderbilt University couldn't replicate the Einstein researchers' earlier results from rodent tests when they did the experiments in dogs. That damped prospects of the brain's glucose-lowering ability in larger animals--particularly humans. But now, for the first time, the Einstein researchers have positive human data on the role of the brain in glucose production, giving them plenty of ammo to silence critics and pursue further studies. With a valid target, drug developers can mount their own efforts to discover compounds that can home in on targets in the brain to treat diabetes.
"This study confirms that the brain plays a significant role in regulating glucose production by the liver," lead author Preeti Kishore, assistant professor of medicine at Einstein, said in a statement. "We are now investigating whether this 'brain-to-liver' pathway is impaired in people with diabetes. If so, we may be able to restore normal glucose regulation by targeting potassium channels in the brain."
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