Scientists have known for decades that human islet amyloid polypeptide, or hIAPP, can turn into a proteinlike substance that contributes to Type 2 diabetes, but they hadn’t understood the intricacies of that transformation.
Now, researchers say they’ve identified the steps in the process that creates the dangerous amyloid—and they have found two compounds that can accelerate and slow it.
The biological molecule hIAPP helps regulate blood sugar levels as well as stomach emptying. But when it malfunctions, hIAPP transforms into clumps of amyloid fibrils, which in turn destroy the insulin manufacturers in the pancreas. People with Type 2 diabetes show an accumulation of the amyloid fibrils.
Researchers at the University of Leeds said they found two new compounds known as molecule modulators that could help. One delays the process of hIAPP turning into amyloid fibrils and the other ramps it up, the scientists published this month in the journal Nature Communications.
Described as “chemical tools,” the molecule modulators can give scientists insight into how the amyloid fibrils grow. Further investigation could potentially give new insights into how and why these proteinlike substances become toxic, the researchers said.
With the current findings, scientists and drug developers have “starting points” for creating new drugs that potentially halt or control the amyloid fibril formation, the researchers said.
“The results are also hugely exciting as they open the door to using the same type of approaches to understanding other amyloid diseases, the vast majority of which currently lack any treatments,” said Sheena Radford, Ph.D., professor of biophysics at Leeds, in a statement.
Other commonly known diseases associated with the buildup of amyloid fibrils include Alzheimer’s, Parkinson’s and more than 50 other protein-misfolding diseases.
“Given that the agents of toxicity in amyloid diseases (including T2D) are still unclear, the discovery of small molecules that can either inhibit or enhance the aggregation rate of hIAPP offers important opportunities to delineate the mechanisms of fibril growth and amyloid-associated toxicity, as well as to act as starting points of therapeutic strategies to combat disease,” the researchers wrote in the study.
Scientists have been working for decades to improve treatments for diabetes. University of Alabama at Birmingham researchers studied a small molecule that was able to normalize the blood glucose in rodent models of severe Type 2 diabetes in 2020 and was able to outperform existing diabetes meds metformin and Jardiance at controlling blood sugar.
Meanwhile, on the amyloid front, biopharmas and researchers have spent years trying to prove removing beta amyloid plaques from the brain can help reduce the burden of Alzheimer’s. Biogen won its controversial Aduhelm approval last year based on evidence that it could reduce amyloid buildup.