Targeting glucose metabolism in the brain could lead to new diabetes treatment
.Researchers at Albert Einstein School of Medicine have shown the brain plays an important role in regulating blood sugars in the body.The finding could mean new approaches for treating diabetes using drugs that target the brain instead of the pancreas to regulate glucose.
In 2005 the scientists used rodents to discover activation of potassium channels in the brain sends signals to the liver, which in turn leads to less production of glucose.
The finding couldn’t be replicated in dog studies, making the discovery appear irrelevant to humans. The 2005 finding was also contrary to current thinking that blood sugar is regulated only by the pancreas.
"The brain is the body's only organ that needs a constant supply of glucose to survive, so it makes sense that it would have some say over how much glucose is produced," said study leader Meredith Hawkins, M.D., professor of medicine and director of the Global Diabetes Initiative at Einstein.
"This role for the brain was demonstrated in earlier Einstein studies in rodents, but there was considerable controversy over whether the results could be applied to humans. We hope this study helps to settle the matter.”
This time the researchers tested humans, using a drug called diazoxide, which activates potassium channels in the hypothalamus of the brain. Ten people were tested who did not have diabetes.
The team controlled hormone release from the pancreas to ensure blood sugar levels were being controlled by the brain instead of the pancreas.
After the subjects received the drug, the researchers performed blood tests that revealed significantly less glucose production by the liver.
They also repeated the study in rats and obtained the same results. When they blocked the effect of diazoxide by injecting a potassium channel blocker directly into the brain, the effects of the drug on glucose production in the liver were reversed.
"This study confirms that the brain plays a significant role in regulating glucose production by the liver," said lead author Preeti Kishore, M.B.B.S., assistant professor of medicine.
The researchers are continuing their studies to find whether people with diabetes have impaired glucose metabolism via the “brain-to-liver” pathway. Kishore says it may be possible to treat diabetes by restoring normal blood sugar regulation by targeting potassium channels in the brain.
The discovery could lead to new diabetes treatments with drugs that target the brain and central nervous system instead of the pancreas.
J Clin Invest. doi:10.1172/JCI58035.
"Activation of KATP channels suppresses glucose production in humans"
Preeti Kishore et al.
November 7, 2011