Major role of the intestinal microbiota in the proper functioning of our immune system
Alterations in the intestinal microbiota have been associated with many autoimmune diseases, and in particular type 1 diabetes. The intestinal microbiota (IM) appears to be a relevant therapeutic target against diabetes and we propose to use molecules able of reshape it in order to prevent the development of diabetes. These molecules naturally secreted by cells of the intestinal epithelium belong to the family of antimicrobial peptides and play a major role in the construction and maintenance of a beneficial IM for its host. Thanks to the support of the FFRD, our project aims to determine the role of intestinal antimicrobial peptides in the development of autoimmune diabetes. Our hypothesis is that a defect in the expression of these peptides would lead to an inflammatory IM promoting the development of the disease. Using these peptides to correct the IM could therefore be a relevant therapeutic approach to prevent the onset of autoimmune diabetes in individuals at risk.
Identify dysglycemia in patients with cystic fibrosis (cystic fibrosis) with continuous blood glucose reading
Patients with cystic fibrosis have a broad spectrum of dysglycemia which is associated with the risk of accelerated clinical decline (loss of weight and / or lung function) and the risk of diabetes associated with cystic fibrosis (DACF). However, the current screening test, oral hyperglycemia (OHG), is associated with multiple issues: acceptance by patients and healthcare teams, costs, etc. The support from the FFRD will allow us to conduct a study to establish whether continuous blood glucose reading can simplify screening for DACF and also predict whether patients are at greater risk for weight loss and / or lung function. These results will better answer questions about the use and interpretation of continuous blood glucose reading in clinical practice.
The endoplasmic reticulum (ER) is the organelle in the pancreatic β-cell where insulin is synthesize. ER stress causses β-cell dysfunction and death in monogenic forms of diabetes. In these uncommon types of diabetes, the genetic loss-of-function of one protein perturbs ER stress signaling. In type 2 diabetes, environmental factors such as saturated free fatty acids cause β-cell ER stress. Research has long been hampered by the limited access to human β-cells. With the generous support of the FFRD, we will use the breakthrough of human induced pluripotent stem cell (iPSC) differentiation into β-cells to gain mechanistic insight into β-cell failure induced by ER stress. This novel disease-revelant model will also be used to identify and test therapeutic targets to protect patients’ iPSC-β-cells.
A food supplement to avoid insulin therapy in case of gestational diabetes?
Inositol, an organic molecule naturally present in the human body, is often associated with groupe B vitamins. It is a food supplement which is naturally found in many foods such as fruits (melon, strawberries, citrus), vegetables (cauliflowers, green peas), legumes (red beans, peas, lentils) but also in whole grains, oilseeds and finally in meat. Inositol is an intracellular mediator acting as a second messenger which decreases insulin resistance. There is a myoinositol deficiency in women with gestational diabetes and several randomized studies versus placebo have shown that it reduced by ⅔ or cases of gestational diabetes in women at risk, with a perfect safety profile and with our side effects. Thanks to the support of the FFRD, we started a randomized placebo-controlled study in women with gestational diabetes with the hypothesis of a reduction of at least 50% in the risk of needing insulin therapy during pregnancy to control diabetes. A revolution in the management of gestational diabetes if this hypothesis is confirmed!