Project 466985

Vitamin K is an essential micronutrient known to regulate blood coagulation and bones. Recent clinical observations in humans suggest that partial vitamin K deficiency might be linked to the development of diabetes. However, the biological mechanism by which vitamin K may influence diabetes remains unknown. Beta cell is a unique cell type of the pancreas responsible for the production of insulin. Diabetes is caused by a reduction in the number of beta cells or by a decrease in their capacity to secrete insulin. This research project aims at understanding the function of a new vitamin K-dependent enzyme in pancreatic beta cells and its potential link with the development of diabetes. We have identified UGGT1 as a new vitamin K-dependent enzyme in beta cells. The majority of the tools of the cell are called proteins and they require a precise structure to repair, synthesized and regulate other components of the cells. The role of UGGT1 is to make sure proteins are folded properly. Without UGGT1, the cell accumulates unfolded and inactive proteins, which can impair cell functions and possibly the secretion of insulin by beta cells. Our approach includes the use of genetically modified mice to determine the role of UGGT1 in beta cells. We will also identify which proteins are folded by UGGT1 in beta cells. Altogether, these studies will allow us to find how UGGT1 support the normal function of the beta cell. These studies are required to understand how vitamin K is implicated in the biology of beta cells and how partial vitamin K deficiency contributes to the development of diabetes. In the future, it could offer new therapeutic approaches for diabetes.