Life-changing protein reduces the risk of type 2 diabetes
[Mar. 10, 2023: Ruth Ashton, University of Birmingham]
Scientists at the University of Geneva (UNIGE) have been working for several years on an alternative therapy based on the S100A9 protein. (CREDIT: iStock Photo)
The estimated number of individuals who are deemed obese is raising at an alarming rate with an expected 1 billion adults and 206 million children worldwide predicted to be clinically obese by 2025, making obesity and obesity-related diseases the major global health challenge. This is coupled with the substantial economic impact of these diseases, estimated as 2.19% of global gross domestic product or ~US$1900 billion globally in 2019.
Research published today shows that a peptide (small protein) 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 researchers 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.
The research team was led by Dr Helen MCGettrick and Dr Asif Iqbal from the University of Birmingham's Institute of Inflammation and Ageing and Institute of Cardiovascular Sciences. Dr McGettrick 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.
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.
Obesity causes complex and dramatic changes in metabolism in adipose (fat) tissue, damage to the pancreas, reduced insulin sensitivity and eventually the hyperglycaemia that underpins type 2 diabetes. It also causes a low-level inflammatory response across the boyd, encouraging white blood cells to enter into many tissues including the visceral adipose tissue (fat stored deep inside the body wrapped around the organs, including the liver and gut) and peritoneal cavity (a thin membrane that encompasses the gut).
The latest research, published in Clinical and Experimental Immunology, shows 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.
Graphical abstract: Dysregulation of leukocyte trafficking, lipid metabolism, and other metabolic processes are the hallmarks that underpin and drive pathology in obesity. (CREDIT: Clinical and Experimental Immunology)
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.”
Prophylactic treatment with PEPITEM reduced leukocyte trafficking induced by 6 weeks of a high-fat obesogenic diet. Schematic representation of experimental time course where wild-type male mice were prophylactically implanted with a mini pump, which continuously released 0.0822 mg/week of PEPITEM or PBS (as a control), and fed HFD for 6 weeks. (CREDIT: Clinical and Experimental Immunology)
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.”
University of Birmingham Enterprise had already filed patent applications covering PEPITEM compositions and therapeutic uses, and has now filed a further application covering its use in the use in the prophylaxis or treatment of obesity-associated inflammatory conditions including chronic low-grade systemic inflammation and pancreatic beta-cell damage.
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Note: Materials provided by University of Birmingham. Content may be edited for style and length.
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