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Canadian researchers have discovered a novel role for vitamin K and gamma-carboxylation in beta cells, as well as their possibly protective role in diabetes, a first in 15 years of basic study.
The discovery by scientists at Université de Montréal and its affiliated Montreal Clinical Research Institute (IRCM) represents a significant step forward in understanding the mechanisms driving diabetes, a disease that affects one in every eleven people globally and has no treatment.
The discovery, which was published on May 11 in Cell Reports, explains, at least in part, how vitamin K helps prevent diabetes and could lead to new therapeutic uses for type 2 diabetes.
Vitamin K is a vitamin known for its function in blood clotting, specifically in gamma-carboxylation, an enzyme reaction required for the process. For many years, it has been thought that this vitamin, and hence gamma-carboxylation, may have additional activities.
Several studies imply a link between low vitamin K intake and an increased risk of diabetes. However, the biochemical processes by which vitamin K protects against diabetes were previously unknown.
Enzymes in Massive Quantities
In their study, UdeM associate research professor of medicine Mathieu Ferron and his team at the IRCM discovered that the enzymes involved in gamma-carboxylation and thus in the use of this vitamin were present in large quantities in pancreatic beta cells, the very cells that produce the precious insulin that controls blood sugar levels.
“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,” said Ferron, a leading researcher in molecular biology. “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.”
“We were able to identify a new gamma-carboxylated protein called ERGP,” added Julie Lacombe, who conducted the work in Ferron’s laboratory. 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.”
A unique vitamin K-dependent protein has been found for the first time in 15 years, opening up a new path of research in this area.
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