Enlightening work from the IRCM.
From left to right: Mathieu Ferron, Julie Lacombe and Kevin Guo.
In a welcome advance in the understanding of the mechanisms underlying diabetes, a disease that affects 1 in 11 people worldwide and has no cure, a research team at the Montreal Clinical Research Institute (IRCM) has identified a new role for vitamin K and gamma-carboxylation in beta cells and their potentially protective role in diabetes, achieving a first in 15 years of basic research. The results of this research are published in the journal Cell Reports.
Vitamin K is an essential micronutrient, known for its role in blood clotting, in particular in gamma-carboxylation, an enzymatic reaction essential to the process. It has been suspected for several years that this vitamin, and thus gamma-carboxylation, may have other functions that are not yet well understood. Several studies suggest a link between a reduced intake of vitamin K and an increased risk of diabetes. However, the biological mechanisms by which vitamin K protects against diabetes remained a mystery until now.
In depth
In this work, Dr. Mathieu Ferron's team was first able to determine that the enzymes involved in gamma-carboxylation and therefore in the use of vitamin K were present in large quantities in pancreatic beta cells, the very cells that produce the precious insulin that controls blood sugar levels. Dr. Ferron is also Associate Research Professor, Department of Medicine (accreditation in molecular biology, and in biochemistry and molecular medicine), at Université de Montréal.
“Diabetes is known to be caused by a reduction in the number of beta cells or by their inability to produce enough insulin, hence our keen interest in this novel finding. In order to elucidate the cellular mechanism by which vitamin K maintains beta cell function, it was essential to determine which protein was targeted by gamma-carboxylation in these cells," said Dr. Mathieu Ferron, a leading researcher in molecular biology.
“We were able to identify a new gamma-carboxylated protein called ERGP. Our study shows that this protein plays an important role in maintaining physiological levels of calcium in beta cells in order to prevent a disturbance of insulin secretion. Finally, we show that vitamin K through gamma-carboxylation is essential for ERGP to perform its role," adds Dr. Julie Lacombe, who conducted this work in Dr. Ferron's laboratory.
Why you should care
This work explains, at least in part, how vitamin K helps prevent diabetes, a disease that weighs heavily on our modern societies. Ultimately, this discovery could lead to new therapeutic applications involving vitamin K or ERGP for type 2 diabetes.
More fundamentally, this is the first time in 15 years that a novel vitamin K-dependent protein has been identified, opening a new field of research in the vitamin K field.
Acknowledgements
This work was performed in the laboratory of Dr. Mathieu Ferron by Dr. Julie Lacombe (research associate) and Kevin Guo (PhD student). We thank several other students of the team who contributed to this research: Jessica Bonneau, Sarah Muir, Sorraya Hezzaz and Florent Gioanni. Denis Faubert, in charge of the mass spectrometry and proteomics platform was also involved. Finally, Alexis Vivoli and his supervisor Dr. Vincent Poitout of the CR-CHUM collaborated in this study.
Thanks also to the Canadian Institutes of Health Research, Diabetes Canada, Diabète Québec, Canada Research Chairs, NSERC (Kevin Guo grant), IRCM, the CMDO network of the FRQS and the NIH.
