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Rates of diabetes are lower in high-altitude places, however scientists have actually been not sure why. Now, a brand-new research study in mice exposes a possible description: Red blood cells, which play a critical function in carrying oxygen throughout the body, might reduce blood sugar level by transforming glucose into a substance that assists release oxygen into tissues.
If the outcomes can be reproduced in individuals, they likewise hint that drugs in early-stage advancement might possibly simulate this path.
Greater elevation, lower blood glucoseIt’s widely known that individuals living at high elevations with low oxygen levels, such as the Andes and the Himalayas, tend to have lower rates of diabeteshowever the factor for the link has actually not been clear. In a 2023 research studyresearchers observed the exact same phenomenon in mice: When the mice were exposed to low-oxygen conditions, they established a condition called “hypoxia,” which takes place when oxygen supply to tissues is inadequate, and their blood sugar likewise dropped.
The vanishing glucose could not be described by the quantity of glucose soaked up by the muscles and other organs in the scans, so it wasn’t clear where it was going.
From high elevations to laboratory chambersTo check whether red cell was accountable for decreasing glucose, the research study authors exposed mice to low-oxygen chambers including 8% oxygen. This imitated high-altitude air, while another group of mice was kept in air with 21% oxygen, which simulated regular climatic conditions, Jain stated.
After a number of weeks, both groups of mice were offered glucose injections, and their blood sugar level levels were determined in time. Compared to the mice in regular oxygen environments, the mice in low-oxygen conditions revealed a much smaller sized spike in their blood sugar level levels, recommending that they might clear glucose from their blood quicker. This impact continued for weeks, even after the animals were gone back to regular oxygen levels, recommending that a low-oxygen environment had a long lasting effect on metabolic process, specialists stated.
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The scientists likewise took imaging scans to track just how much glucose was being soaked up by significant organs and tissues, such as the liver and muscles. A big portion of the vanishing glucose might not be accounted for. This triggered them to examine whether cells in the flowing blood itself may be taking in the glucose.
To check this concept even more, they controlled red-blood-cell numbers straight. The group occasionally gotten rid of blood in oxygen-deprived mice to keep red-blood-cell levels near typical, and discovered that doing so removed the glucose-lowering result of hypoxia. On the other hand, transfusing red cell into mice breathing typical air triggered blood sugar levels to fall, recommending that the variety of red cell alone drove down glucose levels.
Next, the group injected mice with identified glucose and tracked it through the body. They discovered that red cell from the oxygen-deprived mice taken in significantly more glucose than those from the contrast mice. The mice in low-oxygen conditions quickly transformed glucose into a particle that binds to hemoglobin, the protein in red cell that brings oxygen. This binding forces hemoglobin to launch oxygen more quickly into tissues when oxygen levels are low.
The scientists utilized identified glucose particles, like the ones highlighted here, to track how the red cell processed the sugar at greater elevations. (Image credit: Maciej Frolow/Getty Images)Additional analysis revealed that red cell produced in the oxygen-deprived mice likewise consisted of greater levels of a protein called GLUT1, which rests on the cell membrane and assists glucose go into the cell. These red cell had about two times as much GLUT1 and used up approximately 3 times more glucose than typical red cell. By identifying existing red cell before exposing the mice to low-oxygen conditions, the scientists validated that just the brand-new cells produced under low-oxygen conditions revealed these adjustments.
Setting off an uptick in red blood cells, the research study reveals that the cells are structurally altered to take in more sugar in low-oxygen environments, stated Daniel Tennanta hypoxia and metabolic process scientist at the University of Birmingham who was not associated with the work.
Lars Kaestnera red cell biologist at Saarland University in Germany who was not included with the research study, kept in mind that red cell are understood to increase in number when the air is thin, to enhance oxygen transportation around the body. Red cell utilize glucose as fuel. It’s not unexpected that low-oxygen conditions lead to decrease blood glucose levels, as more red blood cells are there to clear it, he informed Live Science.
“From a systemic point of view, this makes a lot of sense,” he said.
It’s an “evolutionarily saved restorative system” to essentially better oxygenate the body at high altitudes, Tennant told Live Science.
It opens the door to thinking about diabetes treatment in a fundamentally different way.
Isha Jain, biochemist at the Gladstone Institutes and the University of California, San Francisco
The body increases its red-blood-cell count at high altitudes by changing the expression of genes that control metabolism and producing more of a hormone called erythropoietin, which triggers the bone marrow to churn out more red blood cells, said Sonia Rocha, a biochemist at the University of Liverpool who was not involved in the study.
This is why elite athletes train in high-altitude areas for their competitions: Their bodies make more red blood cells and thus achieve “more effective flow to disperse oxygen to their tissues,” she told Live Science.
A diabetes drug that mimics oxygen deprivation?
In another experiment, the researchers treated mice with HypoxyStat, an experimental compound that was developed in Jain’s lab and increases how strongly hemoglobin binds to oxygen, preventing its release and mimicking hypoxia. The idea is that mimicking oxygen deprivation with a drug could boost red-blood-cell counts and help regulate blood sugar levels.
However, much more testing is needed before a drug like HypoxyStat could be tested in humans, Rocha noted.
While transfusing red blood cells is not a practical therapy for diabetes, the findings suggest potential directions such as engineering RBCs that act as better glucose sinks, the authors suggest. “It opens the door to thinking about diabetes treatment in a fundamentally different way,” Jain said in a statement.
Martí-Mateos, Y., Safari, Z., Bevers, S., Midha, A. D., Flanigan, W. R., Joshi, T., Huynh, H., Desousa, B. R., Blume, S. Y., Baik, A. H., Rogers, S., Issaian, A. V., Doctor, A., D’Alessandro, A., & & Jain, I. H. (2026 ). Red cell work as a main glucose sink to enhance glucose tolerance at elevation. Cell Metabolism, 38( 3 ), 529-545. e8. https://doi.org/10.1016/j.cmet.2026.01.019
Zunnash Khan is a mechatronics engineer and a science reporter from Pakistan. She has actually composed for Science, The Scientist and Brainfacts.org, to name a few outlets.
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