The majority of cases of type 2 diabetes are related to failure of insulin action in the body. However, for decades researchers and physicians have been faced with a conundrum: not all who are obese or resistant to insulin develop type 2 diabetes. In fact, many patients who are severely obese never develop the disease. As a result scientists have theorized that an unknown factor is involved in regulating glucose metabolism in the liver, and perhaps the presence or absence of this element might determine who gets the disease.
"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, HSPH 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 researchers also identified a potential therapeutic role for a novel aP2 antibody that neutralizes aP2 activity and corrects type 2 diabetes in mice.
"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.
|Contact: Marge Dwyer|
Harvard School of Public Health