Transforming proteins – how molecules in the pancreas could be contributing to the development of type-2 diabetes 29 April 2022 In the continuing research around what might cause the development of type-2 diabetes, a recent paper published in Nature Communications turns to a mysterious spontaneous reaction in the proteins inside the pancreas. In particular, the paper studies one, ordinarily helpful molecule, that transforms into a distinctly unhelpful one. The molecule is known as human islet amyloid (hIAPP), but through the changes that occur to it, its name and make up to become an abnormal protein ‘clump’ known as an amyloid fibril. A build-up of these amyloid fibrils is often seen in people living with type-2 diabetes. Working alongside insulin inside the pancreas, our digestive systems need hIAPP to regulate blood glucose levels and the amount of food in the stomach. When hIAPP malfunctions, it can become clumps of these amyloid fibrils, which then begin to attack and kill the insulin-producing cells in the pancreas. Once a mysterious occurrence in the body, a research team at the University of Leeds has managed to identify the step-by-step changes that happen in the molecule and result in its toxic transformation. On top of this, they also claim to have discovered two compounds, known as molecule modulators, which can control the transformation of this molecule. They say that one of the compounds delays the change from hIAPP to amyloid fibril, while the other speeds it up. Understanding these compounds is an important step in the development of medicine that could stop or control amyloid fibril formation, and thus help in the treatment of type-2 diabetes. Supervisor of the research, Professor Sheen Radford, is understandably excited by the findings. ‘This is an exciting and huge step forward in our quest to understand and treat … and tackle a major health issue that is growing at an alarming rate.’ ‘The compounds we have discovered are a first and important step towards small molecule intervention in a disease that has foxed scientists for generations.’ Beyond its impact on the development of type-2 diabetes, the presence of amyloid fibrils is also believed to be linked to a range of other conditions, including Alzheimer’s Disease and Parkinson’s Disease. ‘The results are 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’, Radford says. For thirty years, this transformation has been something that scientists have sought to understand. This study’s findings are an exciting step forward in developing more knowledge around the onset of type-2 diabetes. The study in full can be found here. Key points There is a molecule in the pancreas (known as hIAPP) that, upon malfunction, can negatively impact insulin production in the pancreas. People with type-2 diabetes are found to have a build-up of the malfunctioning molecules.The mysteries around this malfunction have been unpicked by a team at the University of Leeds, who have discovered the ways in which the molecule transforms, as well as compounds that slow down and speed up the change.These discoveries can help in the development of medicine for halting or controlling this malfunction, and thus helping to treat type-2 diabetes.