Hormone from Fat May Play Key Role in the Treatment of Type 2 Diabetes

Elevated levels of a hormone released from adipose tissue may be the key link in the development of type 2 diabetes in obese patients….

New research out of the Harvard School of Public Health has identified a unique protein released from adipose tissue that plays a role in the metabolism of glucose by the liver. Understanding the mechanism this protein provides a possible new modality in the treatment of type 2 diabetes.

It is well known that type 2 diabetes has developed as a result of uncontrolled glucose production by the liver and increased insulin resistance. This disease is also linked to obesity but the underlying mechanism that determines which obese patients develop diabetes has not been well understood. The identification of the protein, aP2, may provide the answer in understanding the interaction between adipose tissue and uncontrolled glucose production by the liver.

Senior author Gökhan S. Hotamisligil reported, "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."

The Harvard research group began looking at levels of aP2 in mice and correlating these levels to obese humans. In healthy, normal mice, recombinant aP2 was given to raise the circulating concentrations of the protein to levels seen in obese mice and correlating humans. The increased levels of aP2 stimulated glucose production in the primary hepatocytes of the lean mice resulting in impaired glucose metabolism. The study further looked at the reduction of aP2 protein concentrations in obese and diabetic mice. By neutralizing the actions of aP2 in obese diabetic mice, glucose metabolism by the liver returned to normal. The authors were able to conclude that antagonizing the actions of aP2 leads to better control of glucose production by the liver.

Researcher Haiming Cao was able to sum up the importance of understanding the aP2 protein, "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." Further research is now looking into the development of an aP2 antibody to inhibit the action of this protein on the liver.

Haiming Cao, Motohiro Sekiya,and et al.,Adipocyte Lipid Chaperone aP2 Is a Secreted Adipokine Regulating Hepatic Glucose Production. Cell Metabolism, 2013 DOI: 10.1016/j.cmet.2013.04.012