Discovery of Protein Provides 'Key Link' between Obesity and Type 2 Diabetes

Researchers at Monash University (MU) in Australia have discovered a protein that is a “key link” between obesity and the onset of type 2 diabetes.

MU associate professor Matthew Watt and his team of researchers discovered the novel protein pigment epithelium-derived factor (PEDF), which is released into the bloodstream by fat cells and desensitizes the liver and muscle to insulin. In turn, the pancreas begins producing more insulin, which causes the organ to become overworked, causing it to either slow or stop the production of insulin.

According to an article published in Cell Metabolism, acute PEDF administration in lean mice “activated the proinflammatory serine/threonine kinases c-Jun terminal kinase and extracellular regulated kinase in both muscle and liver, which corresponded with reduced insulin signal transduction.” For the lean mice, prolonged exposure to PEDF also “stimulated adipose tissue lipolysis, resulted in ectopic lipid deposition, and reduced insulin sensitivity.” In obese mice, neutralization of PEDF enhanced insulin sensitivity.

"Our research was able to show that increasing PEDF not only causes Type 2 diabetes like complications but that blocking PEDF reverses these effects,” said Watt. “The body again returned to being insulin-sensitive and therefore did not need excess insulin to remain regulated."

In the abstract in Cell Metabolism, the researchers said that the discovery identifies “a causal role for PEDF in obesity-induced insulin resistance.” Watt said that the discovery of the link is a “significant breakthrough” in explaining why obesity can become a trigger for Type 2 diabetes.

“Until now scientists knew there was a very clear pattern and had strong suspicions that a link existed between the two conditions, but our understanding of the chain of events that are caused by the release of PEDF shows a causal link," he added.

The researchers said that knowledge of the link will also be helpful in developing new drugs to treat diabetes.

“We already know that weight-loss generally improves the management of blood glucose levels in diabetes patients,” Watt explained. “Researchers can now move forward knowing this link exists and we can begin to design new drugs to improve the treatment of Type 2 diabetes.”