Type 1 diabetes is a chronic disease caused by the destruction by the patient’s own immune system of the cells responsible for insulin production – the known beta cells of the pancreatic islets. Consequently, since this insulin is the hormone responsible for the cells to capture glucose from the blood to produce energy, the bloodstream ends up carrying an excess of glucose, which ends up causing damage to multiple organs in the body. The result is that in spite of advances made in the treatment of the disease, patients still have a significantly lower life expectancy – up to 12.2 years less than the general population. And in this context, researchers at the Federal Polytechnic School in Lausanne seem to have found a key protein that triggers the immune system to attack and destroy insulin-producing cells, opening the door to the development of new therapies to make In the face of this devastating disease.
According to Steinunn Baekkeskov, director of this research published in the journal “Diabetes”, “the attack by the immune system in type 1 diabetes could be triggered by proteins released by the pancreas itself, as well as by the packaging of these proteins. A finding that could have very significant implications for the design of new therapeutic strategies”.
The study, carried out both with human cell cultures and with an animal model – rats – of type 1 diabetes, shows that beta cells from pancreatic islets are responsible for the release of three proteins that are directly associated with the onset of Type 1 diabetes. In fact, these three proteins are already used by doctors today, once their presence is confirmed, to diagnose the disease. What was not known is that they were released by the pancreas cells themselves.
But, exactly, what is the relationship between these proteins and type 1 diabetes? Simply put, they activate the immune system to attack the cells that have released them. However, it is not just about their presence. Its ‘presentation’ is also very important: proteins must be released into small vesicles called ‘exosomes‘ that expel cells to communicate with their neighbors – but it is also possible that they do so to get rid of unnecessary proteins.
That is, these exosomes with the ‘packaged’ proteins would act as a signal that the beta cells would use to become target of the immune system. Or put another way, to self-destruct.
Specifically, and as the new study shows, the sequence would be as follows: firstly, and in stressful situations, insulin-producing cells release a large amount of exosomes, in which membranes are proteins that activate the immune system. And secondly, and after detecting the presence of these ‘proinflammatory’ proteins in the exosomes, the immune cells attack and destroy their source, thus depriving the body of all production of insulin. The result, the development of type 1 diabetes.
The next step will be to develop exosomes similar to those produced by beta cells, but with one caveat: instead of presenting these proinflammatory proteins, they will contain synthetic molecules that inhibit the action of the immune system.
As the authors conclude, “we hope that our results will lead to new directions in the development of more effective treatments. These synthetic molecules would be picked up by the patient’s immune cells and would prevent attack on the beta cells”.