Red blood cells absorb glucose at high altitude, protecting against diabetes

People living in the mountains have long been healthier when it comes to diabetes. For decades, scientists knew this was real—the data was clear. But nobody could explain why.

Now researchers at Gladstone Institutes have found the answer, and it's hiding in plain sight: your red blood cells.

When oxygen becomes scarce at high elevations, red blood cells shift into a different mode. They start pulling glucose directly from your bloodstream at a dramatically increased rate, acting like tiny sugar sponges. This keeps blood sugar levels low—exactly the opposite of what happens in diabetes. The discovery, published in Cell Metabolism, reveals that red blood cells are far more than simple oxygen delivery trucks. They're metabolic workers that can adapt their behavior based on how much oxygen is available.

The Missing Piece

Isha Jain's lab at Gladstone had been studying what happens to the body when oxygen drops, but they kept hitting a wall. When they gave mice a sugar meal in low-oxygen conditions, the glucose vanished from their bloodstream almost instantly. Yet when they looked at where it was being used—muscle, brain, liver—they found nothing. The sugar was disappearing somewhere, but the usual suspects weren't responsible.

Using advanced imaging, they finally saw it: the red blood cells themselves were absorbing the glucose. Under low oxygen, each red blood cell was consuming far more sugar than normal, and the body was also producing more red blood cells overall. Together, these changes created what amounts to a biological glucose trap.

The mechanism makes sense once you know it. When oxygen is scarce, red blood cells need glucose to produce a molecule that helps release oxygen more efficiently to tissues. It's an elegant adaptation—the body solves an oxygen problem by recruiting red blood cells to clear sugar from the blood. The side effect is remarkably protective against diabetes.

What surprised the researchers most was the scale of the effect. "Red blood cells are usually thought of as passive oxygen carriers," said 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."

From Mountains to Medicine

The real breakthrough came when the team tested whether they could recreate this effect without living at altitude. They used a drug called HypoxyStat, developed in Jain's lab, that mimics low oxygen by making hemoglobin hold onto oxygen more tightly. In diabetic mice, the drug completely reversed high blood sugar and outperformed existing treatments.

Even more striking: the metabolic benefits lasted for weeks or months after mice returned to normal oxygen levels. The body's adaptation seemed to stick around.

The implications stretch beyond diabetes. The same mechanism could matter for athletes—changes in red blood cell metabolism affect how muscles perform during exercise. It could also help trauma patients, where oxygen deprivation after injury is a major cause of death in younger people. Understanding how to leverage these cellular adaptations might open new treatment paths for conditions we haven't yet connected to glucose metabolism.

"There's still so much to learn about how the whole body adapts to changes in oxygen," Jain said. The discovery suggests we've been underestimating what our red blood cells can do.