Proteins are the cell’s workhorses. These macromolecules are made up of long chains of amino acids which fold into specific three-dimensional structures. Sometimes, however, they fold incorrectly and aggregate into long fibres called amyloids. Once the amyloids accumulate, they can cause diseases. This happens, for example, in the brains of people with Alzheimer's (which develop amyloid plaques). Protein aggregation can also cause diabetes type 2, which is characterised by a deposition of islet amyloid polypeptide (IAPP) in the pancreas. Now, a team of scientists led by Professor Pernilla Wittung Stafshede has unearthed a previously unknown role of exosomes in the development of the disease.
“What we’ve found is that exosomes secreted by the cells in the pancreas stop that process in healthy people and protect them from type 2 diabetes, while the exosomes of diabetes patients do not,” says Professor Wittung Stafshede. What the study shows is that “healthy” exosomes bind the protein that causes diabetes on the outside, preventing it from aggregating. However, the results do not explain why. We also don’t know if type 2 diabetes is caused by “sick” exosomes or if the disease itself causes them to malfunction.
“The next step is to make controlled models of the exosomes, whose membranes contain lipids and proteins, to understand exactly what component affects the diabetes protein. If we can find which lipid or protein in the exosome membrane leads to that effect, and can work out the mechanism.”
The study is actually a part of industrial doctoral student Diana Ribeiro’s thesis work, and a collaboration between Chalmers University and the pharmaceutical company Astrazeneca.
“She [Ribeiro] came up with the idea for the project herself,” says Prof Wittung Stafshede, who is Ribeiro’s academic advisor at Chalmers. “She had done some research on exosomes before and I had read a bit about their potential. It’s a fairly new and unexplored field, and honestly I didn’t think the experiments would work. Diana had access to pancreatic cells through Astrazeneca – something we’d never had access to before – and she conducted the studies very thoroughly, and this led us to our discovery.”
(© Christian Borg / AcademiaNet)