The first edition of Diabetes Loop (2015) attracted 562 walkers and runners. This beautiful and festive day of sports has allowed us to donate € 1,200 to the Search for Diabetes. The successful project is that of Mark Diedisheim (physician diabetologist at Cochin Hospital, Paris14è) working on the dedifferentiation of pancreatic beta cell.
Summary on Diedisheim Marc and his team on the dedifferentiation of pancreatic beta cell. It has long been considered as type 1 diabetes was the result of the complete and final destruction of pancreatic beta cells, which are specialized cells in the production of insulin. However, it was recently discovered that some of these cells were present in the pancreas in individuals decades after diagnosis. Their research involves:
- 1- understanding the mechanisms allowing these cells to escape the initial destruction
- 2- see if we can act on these mechanisms in the initial phase to allow a greater number of cells escape destruction, and distance to enable them to rebuild insulin.
Type 1 diabetes is expressed by an increase in blood glucose and decreased insulin production by the pancreas, following a progressive destruction of pancreatic beta cells, specialized cells in the production of insulin. This destruction is of autoimmune origin: the immune system, which defends the body against infections, specifically will destroy beta cells. This process of destruction has long been regarded as progressive total and in the months following the diagnosis of type 1 diabetes, however, today there are biological and anatomical arguments proving the presence in some type 1 diabetic individuals, cells insulin producing beta several years or even decades after diagnosis of the disease.
However, these cells are insufficient to provide normal insulin production, not allowing the stop insulin injections. Understanding the mechanisms allowing certain beta cells to escape the immune system is fundamental,
on the one hand to better understand the mechanisms of type 1 diabetes, the other to consider restoring sufficient producing beta cells' insulin. We know today that the beta cells are highly differentiated cells,
that is to say, very specialized, enabling them to produce and secrete insulin. Our working hypothesis is that some beta cells will lose this differentiation state at the outbreak of type 1 diabetes, enabling them to become "invisible":
these undifferentiated cells not expressing specific markers of pancreatic beta cell, are no longer recognized as such by the immune system and thus escape destruction. Then, several years after the onset of the disease, these surviving cells redifférencieraient into mature beta cells, and reproduce again insulin.
This dedifferentiation mechanism of beta cell is well established in some models of diabetic rodents, but is only a hypothesis in humans today. In our research unit, we have developed an in vitro model of dedifferentiation from human pancreatic beta cells produced in large quantities in the laboratory. We have identified several factors, including a mixture of inflammatory cytokines (molecules synthesized by the cells of the immune system), which induced a dramatic decrease of the insulin production and more specific markers of beta cell. This model now allows us to study which factors are expressed in a cell dedifferentiated beta, and what mechanisms are involved. Eventually, the data generated should enable us to better define the mechanisms of dedifferentiation of beta cells in diabetes 1, and may open the way to new therapeutic targets.