New hormone may aid diabetes treatment

Harvard researchers have discovered a hormone in fat cells that helps regulate how blood glucose is controlled and metabolised in the liver, paving way for new treatments for diabetes.

Using experimental models and state-of-the-art technology, the scientists found that switching off this protein leads to better control of glucose production from the liver, revealing a potential new target that may be used to treat type 2 diabetes and other metabolic diseases.

"Although it has long been recognised that a key event leading to development of type 2 diabetes is uncontrolled glucose production from the liver, underlying mechanisms have been elusive," said senior author Gokhan S Hotamisligil.

"We now have identified aP2 as a novel hormone released from fat cells that controls this critical function," said Hotamisligil.

The ability of one organ - in this case, the adipose tissue - to so directly and profoundly control the actions of another - the liver - is in itself very exciting, said Hotamisligil.

"We suspect this communication system between adipose tissue and liver may have evolved to help fat cells command the liver to supply the body with glucose in times of nutrient deprivation.

"However, when the engorged fat cells lose control over this signal in obesity, the blood levels of aP2 rise, glucose is poured into the bloodstream and cannot be cleared by other tissues. The result is high blood glucose levels and type 2 diabetes," he said.

"It was surprising to find that a critical hormone playing a pathological role in diabetes turned out to be the secreted form of aP2, which for decades has been considered a protein that resides inside the fat cells," said Hotamisligil.

In the new study, researchers first increased the levels of aP2 in normal, healthy mice to match the high blood aP2 levels seen in obese mice and humans. This resulted in impaired glucose metabolism.

Next, they reduced the blood aP2 levels in obese and diabetic mice to low levels seen in lean healthy mice. This intervention restored glucose metabolism to its normal status.

Therefore, the investigators reached the conclusion that the amount and action of aP2 in blood was critical for diabetes, opening up new avenues for potentially being able control or prevent type 2 diabetes.

"The consequences of this discovery are profound, and the potential therapeutic applications by switching this protein off have the capability to reshape the way physicians treat diabetes," said lead author Haiming Cao, postdoctoral fellow in the Department of Genetics and Complex Diseases at HSPH.

The study was published in the journal Cell Metabolism.