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Discovery of glucose sensor in brain may lead to new diabetes treatments

Date: Aug-01-2014
There is an enzyme in the brain that plays a key role in sensing and controlling levels

of glucose in the blood. The underlying mechanism that it triggers appears to link to both type 1

and type 2 diabetes, according to US researchers, who suggest the discovery could lead to new

treatments for diabetes.

They report how they discovered the part played by the enzyme - known as prolyl endopeptidase
(PREP) - in the Proceedings of the National Academies of Sciences (PNAS).

There are two types of diabetes. Type 1 is where the body's ability to make insulin - an

enzyme that helps cells convert glucose into energy - is impaired due to loss of insulin-producing cells in the pancreas. Type 2 arises not through lack of insulin, but because cells

lose their ability to use it properly and become insulin-resistant.

The study found PREP links to both types of diabetes - one way involves communication with the

pancreas, and the other way involves sensing levels of glucose in the blood.

Enzyme triggers series of steps that control glucose levels

Lead author Sabrina Diano, a professor in the Departments of Obstetrics, Gynecology &

Reproductive Sciences, Comparative Medicine, and Neurobiology at Yale University School of

Medicine, New Haven, CT, says they discovered that PREP - found in a part of the

hypothalamus known as the ventromedial nucleus - triggers a series of steps that control glucose

in the blood.

Researchers say they have discovered an enzyme in the brain that plays a key role in sensing and controlling levels of glucose in the blood.

The team already knew that the ventromedial nucleus has brain cells that are capable of

sensing glucose, and wanted to find out more about the link to PREP.

They discovered that PREP gives brain cells in this part of the brain the ability to sense

glucose. When the cells detect rising glucose levels, they instruct the pancreas to secrete more

insulin, which keeps glucose in check and prevents diabetes.

When they genetically engineered mice with low levels of the enzyme, they found the mice had

high levels of blood glucose and developed diabetes.

They confirmed the effect of reduced PREP by treating normal mice with a PREP inhibitor. The

mice showed decreased insulin levels and impaired glucose tolerance.

And when they restored PREP function in the mice bred to have low PREP - by injecting them

with a virus that causes the relevant gene to be switched on again - they found it reversed the

glucose intolerance the mice had shown before.

Low levels of PREP prevent neurons sensing increases in glucose

Prof. Diano says the low levels of enzyme prevented the neurons from sensing increased levels

of blood glucose, which in turn meant they could not control release of insulin from the

pancreas, which led the mice to become glucose intolerant and diabetic.

She and her colleagues conclude that:

"Taken together, our results unmask a previously unknown

player in central regulation of glucose metabolism and pancreatic function."

If they find the targets in the enzyme that make the neurons sense changes in glucose levels,

then the researchers believe it could lead to a new type of drug to regulate insulin secretion.

Such a drug could not only treat type 2 diabetes, but perhaps even prevent it, says Prof. Diano.

Funds from the National Institutes of Health and the American Diabetes Association helped to

finance the study.

Meanwhile, another recently published study from China found that shift work may increase risk for type

2 diabetes, particularly in men. While the researchers who carried out the meta-analysis did

not examine why the risk is higher in men, they suggest it could be that repeated disruption of

the body's internal clock affects levels of testosterone in men. Other studies have shown low

levels of the male hormone are linked to insulin resistance and diabetes.

Written by Catharine Paddock PhD

View all articles written by Catharine, or follow her on:

Courtesy: Medical News Today
Note: Any medical information available in this news section is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional.