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Grant: Project Grant

Institut de recherches cliniques de Montréal

$795,600.00

Role of vitamin K-dependent gamma-carboxylation in beta cell and diabetes

FY 2020-21

Summary
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 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 capacity of human and mouse beta cells to respond to stress. 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.
Program
Project Grant
Location
Quebec, Canada
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
433007
Name
Ferron Mathieu
Region
Québec
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Nutrition, Metabolism and Diabetes
Theme2
Biomedical
Prcname2
Diabetes, Obesity, Lipid & Lipoprotein Disorders
Projecttitle
Role of vitamin K-dependent gamma-carboxylation in beta cell and diabetes
Programtype2
Operating Grants
Orgnameinp2
Institut de recherches cliniques de Montréal
Cihramount2
$795,600
Cihrequipment2
$0
Programname2
Project Grant
Keyworddelim
Diabetes & Beta Cell Dysfunction; Endoplasmic Reticulum; Er Stress; Unfolded Protein Response; Gamma-Carboxylation & Ggcx; Glucose; High Fat Diet; Insulin; Insulin Secretion; Pancreatic Beta Cells & Pancreatic Islets; Protein Folding; Uggt1; Vitamin K; Vitamin K-Dependent Protein
Abstract
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 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 capacity of human and mouse beta cells to respond to stress. 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.
Competitiondate
202010
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Ferron, Mathieu
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $795,600~ $0~