The red blood cells supply our body with oxygen. But apparently their function goes far beyond that: as a study now shows, they also play an important role in the regulation of blood sugar. Especially when there is a lack of oxygen, red blood cells absorb large amounts of glucose and convert it into a molecule that helps them deliver the remaining oxygen to the tissue particularly efficiently. As a positive side effect, they also lower blood sugar levels. The findings could provide an explanation for why people who live at high altitudes with thin air are less likely to develop diabetes.
Our red blood cells, also called erythrocytes, are tiny cells that consist almost entirely of the oxygen-binding blood pigment hemoglobin. They are produced in the bone marrow and, when mature, have neither a cell nucleus nor mitochondria. They get their energy by breaking down glucose without using oxygen. Until now, little attention has been paid to their influence on blood sugar levels. Instead, in scientific terms, red blood cells have usually been reduced to their function as oxygen transporters.
Mysterious sugar loss
But erythrocytes apparently also play a crucial role in glucose metabolism – and the less oxygen the air we breathe contains, the more so. This is the conclusion reached by a team led by Yolanda Martí-Mateos from the Gladstone Institutes in San Francisco. It all started with a surprising observation in mice exposed to oxygen-poor air: “When we gave the mice sugar while they were hypoxic, it disappeared from their bloodstream almost immediately,” reports Martí-Mateos. “We examined muscles, brain, liver – all the usual suspects – but nothing in these organs could explain what was going on.”
Finally, the researchers found the major sugar consumers: red blood cells. When there is a lack of oxygen, their amount increases sharply in order to continue to supply the body’s tissues with the vital breathing gas. However, if the team prevented this increase by regularly taking blood from the hypoxic mice, the massive glucose consumption did not occur. Conversely, mice kept under normal conditions consumed more glucose when the researchers injected them with additional red blood cells.
Help with oxygen supply
Further experiments revealed that the mice not only produced more red blood cells when oxygen was deprived, but that these newly formed red blood cells also consumed more glucose than those produced during periods of sufficient oxygen supply. According to the study, this is caused by a protein called GLUT1, which sits on the cell membrane of red blood cells and is responsible for the transport of glucose into the cells. The erythrocytes formed under hypoxic conditions had significantly more of these transport proteins and were therefore able to absorb more glucose in a shorter time.
But what do the blood cells do with the sugar? Martí-Mateos and her team found an answer to this too. “The hypoxic erythrocytes converted the glucose into a molecule called 2,3-diphosphoglycerate within minutes,” report the researchers. “This molecule binds to hemoglobin and helps deliver oxygen to the tissue – exactly what the body needs when oxygen levels in the air are low.” Due to the increased sugar consumption, the erythrocytes can make optimal use of the little oxygen available. Since each of these blood cells has a lifespan of around four months, the effect persists long after enough oxygen is available again.
From the researchers’ perspective, this could also be a therapeutic approach to treating diabetes. “Red blood cells represent a hidden area of glucose metabolism that has previously been ignored,” says Martí-Mateo’s colleague Isha Jain. “This discovery could open up completely new ways to control blood sugar.” It is already known that people who live at high altitudes with thin air are less likely to develop diabetes. It is possible that the effects of oxygen deficiency could also be replicated with medication.
Source: Yolanda Martí-Mateos (Gladstone Institutes, San Francisco) et al., Cell Metabolism, doi: 10.1016/j.cmet.2026.01.019