Researchers have identified a biological mechanism that may explain why people living at high altitudes have a lower risk of diabetes. A latest study published in Cell Metabolism found that red blood cells can actively absorb excess glucose from the bloodstream under low oxygen conditions, helping lower blood sugar levels and potentially opening new avenues for diabetes treatment. Diabetes affects hundreds of millions of people worldwide and is characterized by chronically elevated blood glucose levels, which can damage organs over time.
Scientists have long observed that populations living at high altitudes tend to have lower rates of diabetes compared to those living at sea level. At high altitudes, oxygen levels in the air are lower, which exposes the body to chronic mild hypoxia. However, the biological mechanism behind this protective effect remained unclear.
The new study, led by researchers at the Gladstone Institutes and the University of California, San Francisco, found that hypoxia triggers metabolic changes in red blood cells. Instead of only transporting oxygen, these cells increase their uptake and use of glucose from the bloodstream.
This process reduces circulating blood sugar levels and may contribute to improved glucose control observed in high-altitude environments. Senior author Dr. Isha Jain, a Gladstone investigator and professor at the University of California, San Francisco, said the findings reveal a previously unrecognized role of red blood cells in regulating blood glucose.
The researchers conducted controlled laboratory experiments primarily in mouse models exposed to low oxygen levels that mimic high-altitude conditions. These preclinical experiments showed that mice exposed to hypoxia had significantly lower blood glucose levels and cleared glucose more efficiently compared to mice in normal oxygen environments.
Initially, researchers expected organs such as the liver, brain, or skeletal muscle to account for the increased glucose utilization. However, metabolic tracing and imaging techniques showed that red blood cells absorbed a substantial portion of the excess glucose.
Under hypoxic conditions, mice produced more red blood cells, and each cell demonstrated increased glucose consumption. This metabolic adaptation supports the production of molecules such as 2,3-bisphosphoglycerate, which helps red blood cells release oxygen more effectively to tissues when oxygen availability is low. At the same time, increased glucose consumption by these cells lowers blood sugar levels.
The findings were based on preclinical animal experiments. The study did not report therapeutic testing in humans.
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The researchers also observed that improved glucose regulation persisted for weeks after mice returned to normal oxygen levels. This suggests that hypoxia induces lasting metabolic changes in red blood cells that continue to influence glucose metabolism even after oxygen levels normalize.
These results identify red blood cells as active regulators of systemic glucose metabolism, functioning independently of traditional insulin-mediated pathways.
The researchers also tested an experimental compound that alters how hemoglobin binds oxygen, simulating some metabolic effects of hypoxia. In mouse models of diabetes, treatment with this compound significantly lowered blood glucose levels and improved glucose tolerance.
The study did not identify the compound as an approved diabetes therapy, and its effects have not yet been confirmed in human clinical trials. The compound was originally developed for other medical applications, and further research is required to determine its safety and effectiveness for treating diabetes.
The findings demonstrate that red blood cells play a more direct role in regulating blood sugar than previously understood. By acting as a glucose sink under hypoxic conditions, these cells help remove excess glucose from circulation and improve metabolic balance.
Researchers suggest that targeting red blood cell metabolism could represent a new therapeutic strategy for diabetes. However, additional studies, including human clinical trials, are necessary before such approaches can be used in routine medical care.
1. Martí-Mateos, Y., et al. 2026. "Red Blood Cells Serve as a Primary Glucose Sink to Improve Glucose Tolerance at Altitude." Cell Metabolism. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(26)00018-5