Grant: Project Grant - PA: Nutrition, Metabolism and Diabetes

Vitamin K is an essential micronutrient known to regulate the activity of proteins implicated in blood coagulation and mineralized tissues. 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 vitamin K-dependent proteins in pancreatic beta cells and its potential link with the development of diabetes. Our approach includes the use of genetically modified mice lacking the components of the vitamin K cycle in pancreatic beta cells. We will analyze these animals to determine the role of vitamin K in protecting beta cells from cell death, and in promoting their proliferation and function. We will also study the interaction between vitamin K and the endoplasmic reticulum stress in human and mouse beta cells. Finally, we will test if vitamin K can improve or prevent diabetes in pre-clinical mouse models. Altogether, these studies will allow us to understand how vitamin K is implicated in the biology of beta cell and how partial vitamin K deficiency contributes to the development of diabetes.