A new potential drug that could treat type 2 diabetes acts like a drawbridge password to let fat cells properly manage glucose, a new study in mice has found.
The new research, published in Diabetes today (13 July 2022), has found that a drug that targets a protein interaction on the surface of adipocytes or ‘fat cells’ may be able to re-establish typical insulin sensitivity, which is a key process in managing type 2 diabetes. These fat cells typically regulate blood glucose by absorbing it and storing it. However, insulin resistance stops fat cells from being able to let in glucose and instead overspill toxic fat, leading to higher blood sugar levels and storage of fat in the wrong place causing a series of other issues.
The team of international researchers, led by Inserm researcher Vincent Marion and his team at the Medical Genetics Laboratory (Inserm/Université de Strasbourg) in collaboration with the University of Birmingham and Monash University, have developed a potential new drug called PATAS, a peptide-derived treatment based on in-depth understanding of complex genetic disease known as Alström syndrome.
PATAS works by targeting a process in fat cells that regulates blood glucose. Two proteins which float around on the exterior of these fat cells are normally link together, and they split apart when insulin is present.
When fat cells become insulin resistant, the protein link stops breaking apart in the presence of insulin, and glucose is blocked from coming in. PATAS works to restore that natural process of breaking the link, allowing fat cells to regain their protective role in blood glucose regulation.
In our studies in cells and with mice, we saw that PATAS works like a passcode to restore usual function, allowing fat cells to effectively lower the drawbridge like it would in the presence of insulin and allow glucose to flow into the cellsDr Tarekegn Hiwot
Dr Tarekegn Hiwot, Consultant Endocrinologist and Inherited Metabolic Disorders at University Hospitals Birmingham NHS Foundation Trust and Honorary Reader, Institute of Metabolism and Systems Research at the University of Birmingham is a co-author of the research. Dr Hiwot said:
“PATAS acts a bit like a key to reset the typical function of fat cells called adipocytes. The key protein that we have studied usually links and unlinks with others to form a natural barrier stopping glucose flowing into the cell, which is then unlocked in the presence of insulin in healthy cells.
“With insulin-resistant cells, the barrier doesn’t break despite the presence of insulin. In our studies in cells and with mice, we saw that PATAS works like a passcode to restore usual function, allowing fat cells to effectively lower the drawbridge like it would in the presence of insulin and allow glucose to flow into the cells.”
Dr Vincent Marion, Director of the Medical Genetics Laboratory at INSERM and lead researcher of the project said:
"Thanks to PATAS, the adipocytes that could no longer access glucose were once again able to absorb it and then metabolize it in order to synthesize and secrete lipids which are beneficial to the entire body.
“These positive effects are visible in our animal models, with a marked improvement in insulin resistance. Other parameters and comorbidities are also improved, including better blood glucose control and decreased liver fibrosis and steatosis."