SAN FRANCISCO—February 19, 2026—Scientists have long observed that individuals residing at high altitudes, where oxygen levels are significantly lower, exhibit lower rates of diabetes compared to those living at sea level. Despite this intriguing correlation, the underlying mechanism remained elusive until now.
Researchers at Gladstone Institutes have unveiled a groundbreaking discovery that red blood cells act as glucose sponges in low-oxygen environments, such as those found on the world’s highest peaks. This revelation, published in the journal Cell Metabolism, demonstrates how red blood cells adapt their metabolism to absorb sugar from the bloodstream. This adaptation not only enhances the cells’ capacity to deliver oxygen efficiently to body tissues but also inadvertently reduces blood sugar levels.
Gladstone Investigator Isha Jain, PhD, the senior author of the study, emphasized the significance of these findings, stating, “Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now. This discovery could open up entirely new ways to think about controlling blood sugar.”
The Hidden Glucose Sink
Dr. Jain has dedicated years to exploring how low blood-oxygen levels, known as hypoxia, influence health and metabolism. In a prior study, her team observed that mice exposed to low-oxygen air exhibited significantly lower blood glucose levels, a hallmark of reduced diabetes risk. However, the destination of the glucose remained a mystery.
Yolanda Martí-Mateos, PhD, a postdoctoral scholar in Jain’s lab and the study’s first author, explained, “When we gave sugar to the mice in hypoxia, it disappeared from their bloodstream almost instantly. We looked at muscle, brain, liver—all the usual suspects—but nothing in these organs could explain what was happening.”
Through advanced imaging techniques, the team identified red blood cells as the missing “glucose sink,” a term used to describe entities that absorb significant amounts of glucose from the bloodstream. This discovery challenged the conventional view of red blood cells as metabolically simple.
Further experiments confirmed that red blood cells in low-oxygen conditions not only increased in number but also absorbed more glucose than those in normal oxygen environments. To unravel the molecular mechanisms behind this phenomenon, Jain’s team collaborated with experts Angelo D’Alessandro, PhD, from the University of Colorado Anschutz Medical Campus, and Allan Doctor, MD, from the University of Maryland.
The researchers demonstrated that in low-oxygen conditions, glucose is utilized by red blood cells to produce a molecule that aids in oxygen release to tissues, a critical function when oxygen is scarce. “What surprised me most was the magnitude of the effect,” D’Alessandro noted. “Red blood cells are usually thought of as passive oxygen carriers. Yet, we found that they can account for a substantial fraction of whole-body glucose consumption, especially under hypoxia.”
A New Path to Diabetes Treatment
The team’s findings extend beyond understanding physiological adaptations. They revealed that the benefits of chronic hypoxia persisted for weeks to months after mice returned to normal oxygen levels. Additionally, the researchers tested HypoxyStat, a drug developed in Jain’s lab to mimic low-oxygen conditions. This pill enhances hemoglobin’s affinity for oxygen, thereby reducing its availability to tissues.
HypoxyStat demonstrated remarkable efficacy in reversing high blood sugar in diabetic mouse models, outperforming existing medications. “This is one of the first uses of HypoxyStat beyond mitochondrial disease,” Jain remarked. “It opens the door to thinking about diabetes treatment in a fundamentally different way—by recruiting red blood cells as glucose sinks.”
The implications of these findings could extend beyond diabetes to fields such as exercise physiology and the management of pathological hypoxia following traumatic injury. D’Alessandro highlighted the potential impact, noting that trauma remains a leading cause of mortality among younger populations, and shifts in red blood cell levels and metabolism may influence glucose availability and muscle performance.
Jain concluded, “This is just the beginning. 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.”
About the Study
The paper, titled “Red Blood Cells Serve as a Primary Glucose Sink to Improve Glucose Tolerance at Altitude,” was published by the journal Cell Metabolism on February 19, 2026. The authors include Yolanda Martí-Mateos, Ayush D. Midha, Will R. Flanigan, Tej Joshi, Helen Huynh, Brandon R. Desousa, Skyler Y. Blume, Alan H. Baik, and Isha Jain of Gladstone; Zohreh Safari, Stephen Rogers, and Allan Doctor of the University of Maryland; and Shaun Bevers, Aaron V. Issaian, and Angelo D’Alessandro of the University of Colorado Anschutz.
The research was supported by the National Institutes of Health, the California Institute for Regenerative Medicine, Dave Wentz, the Hillblom Foundation, and the W.M. Keck Foundation.
About Gladstone Institutes
Gladstone Institutes is an independent, nonprofit life science research organization committed to using visionary science and technology to overcome disease. Established in 1979, it is located in the Mission Bay neighborhood of San Francisco, a hub of biomedical and technological innovation. Gladstone’s unique research model disrupts traditional scientific approaches, funding bold ideas and attracting the brightest minds in the field.
