Published Apr 11, 2026 | 7:00 AM ⚊ Updated Apr 11, 2026 | 7:00 AM
Synopsis: At higher altitudes — think above 5,000 metres — the air contains less oxygen. The body responds by producing more red blood cells to compensate. But the study showed something remarkable: those new red blood cells also absorb far more glucose than normal.
Scientists have long wondered why people living in the mountains, in places like the Himalayas or the Andes, tend to have lower rates of diabetes than those living closer to sea level.
Now, researchers at the Gladstone Institutes in the United States have finally found the answer. And it lies somewhere most scientists never thought to look: inside red blood cells.
The study, published in the journal Cell Metabolism, revealed that red blood cells dramatically increase their uptake of sugar from the bloodstream when oxygen levels are low, quietly acting as a hidden glucose sponge in the body.
“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” said senior author Isha Jain. “This discovery could open up entirely new ways to think about controlling blood sugar.”
At higher altitudes — think above 5,000 metres — the air contains less oxygen. The body responds by producing more red blood cells to compensate. But the study showed something remarkable: those new red blood cells also absorb far more glucose than normal.
In effect, the blood is being quietly “cleaned” of excess sugar by the very cells tasked with carrying oxygen.
When researchers exposed mice to low oxygen, blood glucose fell almost instantly. But when they scanned the major organs, liver, brain, muscle, none of them could explain where all the sugar had gone.
“When we gave sugar to the mice in hypoxia, it disappeared from their bloodstream almost instantly,” said Dr Yolanda Martí-Mateos, first author of the study. “We looked at muscle, brain, liver, all the usual suspects, but nothing in these organs could explain what was happening.”
Around 70% of the increased glucose uptake was unaccounted. The missing culprit, it turned out, was the red blood cell, long considered too simple to play such a role.
Red blood cells have traditionally been thought of as passive transporters, they pick up oxygen in the lungs and deliver it to tissues around the body. They have no nucleus, cannot make new proteins in their mature form, and were not considered significant players in sugar metabolism.
“Red blood cells are usually thought of as passive oxygen carriers,” said Dr Angelo D’Alessandro of the University of Colorado. “Yet, we found that they can account for a substantial fraction of whole-body glucose consumption, especially under hypoxia.”
“What surprised me most was the magnitude of the effect,” he added.
Two things happen when the body is exposed to low oxygen.
First, the body produces significantly more red blood cells. Each new cell is born with higher levels of glucose transporters on its surface, proteins called GLUT1 and GLUT4, giving it roughly two to three times the sugar-absorbing capacity of a cell produced under normal conditions.
Second, even existing red blood cells switch their internal chemistry within minutes. A protein called band 3 normally keeps a key enzyme, GAPDH, locked to the cell membrane in an inactive state. When oxygen drops, a competing molecule nudges GAPDH free, switching on the cell’s sugar-burning machinery almost instantly.
The glucose is then used to make a molecule called 2,3-DPG, which helps haemoglobin release oxygen more efficiently to body tissues, a critical survival adaptation at altitude. Lowering blood sugar is, in a sense, a beneficial side effect.
One of the most striking findings was how long the effect persists. When mice were returned to normal oxygen levels, their improved blood sugar control lasted for weeks to months, long after the low-oxygen conditions had ended.
This is because the newly made red blood cells, born with higher glucose-absorbing capacity, continue circulating in the body. Red blood cells live for roughly 90–120 days, so the benefits linger well beyond the altitude exposure itself.
The team also tested a drug called HypoxyStat, developed in the same laboratory, which tricks the body into behaving as though it is at high altitude. It does this by making haemoglobin cling to oxygen more tightly, reducing how much reaches the tissues, effectively mimicking the low-oxygen state.
In mouse models of both type 1 and type 2 diabetes, HypoxyStat completely reversed elevated blood sugar levels, performing even better than existing diabetes medications.
“This is one of the first uses of HypoxyStat beyond mitochondrial disease,” said Jain. “It opens the door to thinking about diabetes treatment in a fundamentally different way, by recruiting red blood cells as glucose sinks.”
India carries one of the heaviest diabetes burdens in the world, with tens of millions affected. Treatments that work independently of insulin, the hormone that fails or becomes less effective in diabetes, are particularly valuable, since this mechanism appears to work without insulin signalling at all.
The findings also help explain something long puzzling about high-altitude populations. Sherpas, for instance, carry genetic variants that suppress the usual altitude-driven increase in red blood cells, and unlike most other mountain communities, they do not enjoy improved blood sugar control. This fits perfectly with the new mechanism.
Patients with polycythaemia, a condition involving excess red blood cells, tend to have lower blood glucose. Conversely, anaemia, low red blood cell count, is frequently associated with worse blood sugar control and higher diabetes risk.
The researchers cautioned that directly increasing red blood cells through transfusions or similar means carries risks, including thicker blood and cardiovascular strain. A safer future approach, they suggested, could involve promoting faster red blood cell turnover, keeping the pool stocked with younger, more glucose-hungry cells, without raising overall cell counts.
“This is just the beginning,” said Jain. “There’s still so much to learn about how the whole body adapts to changes in oxygen, and how we could leverage these mechanisms to treat a range of conditions.”
For now, the study offers a genuinely new way of thinking about diabetes, one rooted not in the pancreas or insulin, but in the quiet, tireless work of the body’s most abundant cell.
(Edited by Majnu Babu).
