Novel peptide may tackle the root cause of type 2 diabetes

Researchers from the University of Birmingham, UK, showed that a peptide called PEPITEM, could provide a revolutionary approach to reducing the risk of type 2 diabetes and other obesity-related diseases such as hepatic steatosis (fatty liver). 

The scientists used an animal model of obesity to investigate whether PEPITEM, delivered by a slow-release pump, could prevent or reverse the effects that a high fat diet has on the pancreas. 

Excitingly, the results showed that administration of PEPITEM significantly reduced the enlargement of insulin-producing cells in the pancreas and also significantly reduced immune cell migration into various tissues. 

Dr Helen McGettrick from the University of Birmingham’s Institute of Inflammation and Ageing and Institute of Cardiovascular Sciences, said: “We have found a new therapeutic approach that could provide new drugs to tackle the root cause of obesity-related conditions by preventing the damage caused by systemic inflammation”.

Obesity causes complex and dramatic changes in metabolism in adipose tissue, damage to the pancreas, reduced insulin sensitivity and eventually the hyperglycaemia, that underpins type 2 diabetes. 

PEPITEM was first identified in 2015 by Birmingham researchers who described its role in the adiponectin-PEPITEM pathway, which is involved in controlling the onset and severity of auto-immune and chronic inflammatory diseases. 

The latest research, published in Clinical and Experimental Immunology, identifies that the adiponectin-PEPITEM pathway also connects obesity, the low-level inflammatory response that is driven by it, and changes in the pancreas that precede diabetes. 

The results showed that dosing with PEPITEM while the mice were on a high fat diet significantly reduced the enlargement of insulin-producing beta cells in the pancreas and the number of white blood cells in the visceral adipose tissue and peritoneal cavity, compared to controls. 

The researchers also looked at the potential of PEPITEM to reverse the changes brought on by obesity, by feeding the animals a high fat diet prior to treating with PEPITEM. Excitingly, they saw similar results.  Dr Asif Iqbal commented: “Until now we have understood very little about how the inflammation that accompanies obesity drives pathology. 

These results show us that PEPITEM can both prevent and reverse the impact that obesity has on metabolism.  The next stage is to translate these exciting results into therapeutics that can be used in humans.”

Professor Ed Rainger from Birmingham’s Institute of Cardiovascular Sciences led the team that first identified PEPITEM.  He commented: “We are all very excited about these latest results.  PEPITEM is a naturally occurring peptide.  We have already shown it has effects on several organs and now for the first time, we have shown that PEPITEM is effective in a model of a disease process that is not driven by the immune system alone.”