Image from Graham Beards
Platelets (blue dots) surrounded by red blood cells.
New research published in Cell Reports suggests platelets are highly reliant on their ability to metabolize glucose.
Researchers studied mice lacking proteins that platelets use to import glucose—glucose transporter (GLUT) 1 and GLUT3.
These mice had lower platelet counts and their platelets had shorter life spans than platelets in wild-type mice.
“We found that glucose metabolism is very critical across the entire life cycle of platelets—from production, to what they do in the body, to how they get cleared from the body,” said E. Dale Abel, MBBS, PhD, of the University of Iowa in Iowa City.
For this study, Dr Abel and his colleagues studied genetically engineered mouse models that were missing GLUT1 and GLUT3 or GLUT3 alone and observed how platelet formation, function, and clearance were affected.
Mice missing glucose transporter proteins did produce platelets, and the platelets’ mitochondria metabolized other substances in place of glucose. However, the mice had platelet counts that were lower than normal.
The researchers were able to pinpoint 2 causes for the low platelet count in mice lacking GLUT1 and GLUT3—fewer platelets being produced and increased clearance of platelets.
The team tested megakaryocytes’ ability to generate new platelets by depleting the blood of platelets and observing the subsequent recovery, which was lower than normal.
They also tested the megakaryocytes in culture, stimulating them to create new platelets, and found the generation of new platelets was defective.
“Clearly, we show that there’s an obligate need for glucose to bud platelets off from the bone marrow,” Dr Abel said.
In addition, the team observed that young platelets functioned normally, even in the absence of glucose. But as they aged, the platelets were cleared from the circulation earlier than normal because they were being destroyed.
“We identified a new mechanism of necrosis by which the absence of glucose leads to the cleavage of a protein called calpain, which marks them for this necrotic pathway,” Dr Abel said. “If we treated the animals with a calpain inhibitor, we could reduce the increased platelet clearance.”
The team also sought to determine whether platelets could exist and function when mitochondria metabolism is halted.
They injected the mice with oligomycin, which inhibits mitochondrial metabolism. In the mice deficient in GLUT1 and GLUT3, platelet counts dropped to 0 within about 30 minutes. The same effect did not occur in wild-type mice.
“This work defined a very important role for metabolism in how platelets leave the bone marrow, how they come into circulation, and how they stay in circulation,” Dr Abel said. “It could even have implications for why platelets have to be used within a certain period of time when they’re donated at the blood bank—the fresher the better.”
