A new study from Gladstone Institutes reveals that red blood cells function as glucose “sponges” in low-oxygen conditions, explaining why populations living at altitude have a lower incidence of diabetes and paving the way for new treatments.
Scientists have long known that people who live at high altitudes, where oxygen levels are small and have lower rates of diabetes than those living near sea level. However, the mechanism behind this protection remained a mystery.
Now, researchers at the Gladstone Institutes have explained the origins of the phenomenon, discovering that red blood cells work like “sponges” of glucose in low-oxygen conditions, such as those found on the world’s highest peaks.
In new, published this Thursday in the magazine Cell Metabolismthe team demonstrated how red blood cells can alter their metabolism to absorb sugar present in the bloodstream.
At high altitude, this adaptation increases cell capacity to transport oxygen more efficiently to tissues throughout the body, also having the beneficial effect of reducing sugar levels in the blood.
The conclusions solve a long-standing riddle in physiology, says Isha JainPhD, researcher at Gladstone Institutes and senior author of the study, in a statement published on .
“Red blood cells are a hidden factor of glucose metabolism that has so far gone unrecognized,” says Jain, who is also a principal investigator at the Arc Institute and a professor of biochemistry at the University of California, San Francisco. “This discovery could open up entirely new ways of thinking about the blood sugar control“.
The hidden glucose sponge
Jain has dedicated years to studying how low blood oxygen levels, known as hypoxiaaffect health and metabolism.
In a previous study, his team noticed that mice breathing low-oxygen air had lower blood glucose levels. much lower than normal.
This meant that the animals quickly consumed glucose after ingestion of food — a characteristic associated with lower risk of diabetes. However, when researchers turned to imaging techniques to track the fate of glucose, they were unable to explain their whereabouts.
“When we give sugar to hypoxic mice, it disappeared of the bloodstream almost immediately“, account Yolanda Martí-Mateospostdoctoral researcher in Jain’s lab and first author of the study. “We analyzed the muscle, the brain, the liver — the usual suspects — but none of these bodies could explain what was happening.”
Using another technique imagingthe team revealed that red blood cells were the “glucose sponge” missing — expression used to describe any structure that absorbs and consumes large quantities of glucose from the bloodstream. These cells, long considered metabolically simple, seemed unlikely candidates.
Still, additional experiments in mice confirmed that red blood cells were, in fact, absorbing the glucose. Under low-oxygen conditions, the mice not only produced significantly more red blood cells, but each cell absorbed more glucose than those produced under normal oxygenation conditions.
To understand the molecular mechanisms underlying this observation, Jain’s team collaborated with Angelo D’Alessandrofrom the University of Colorado at Anschutz Medical Campus, and with Allan Doctorfrom the University of Maryland, a longtime researcher of red blood cell function.
Researchers have demonstrated that under low oxygen conditions, glucose is used by red blood cells to produce a molecule which helps cells to release oxygen to tissues — something that is needed in greater quantities when oxygen is scarce.
“What surprised me most was the magnitude of the effect“, says D’Alessandro. “Red blood cells are usually seen as passive oxygen transporters. However, we found that they may be responsible for a substantial fraction of whole-body glucose consumption, especially in hypoxia.”
Scientists have also demonstrated that benefits of chronic hypoxia were maintained for weeks to months after the mice returned to normal oxygen levels.
“This is just the beginning,” concludes Jain. “There is still much to learn about how the body adapts to variations in oxygen and how we can harness these mechanisms to treat a wide range of diseases.”
