Tibetans who live in highlands more than 4,000 meters above sea level rarely develop diabetes. Scientists have found the secret. Red blood cells that deliver oxygen throughout the body act like a sponge that absorbs glucose in low-oxygen conditions. If a low-oxygen environment can be created in the human body, it could be used to treat diabetes. The same approach has previously been used to treat a congenital neurological disorder.
A team led by Isha Jain at the Gladstone Institutes in the United States said on the 20th in the international journal Cell Metabolism that "red blood cells become a sponge that absorbs glucose in low-oxygen environments like the world's highest peaks, strengthening their ability to deliver oxygen and, as a side effect, lowering blood sugar levels."
◇ Tibetans' diabetes rate is one-third that of Han Chinese
Scientists have long known that people living at high altitudes with low oxygen concentrations have a lower incidence of diabetes than those living near sea level. According to China's Center for Disease Control and Prevention in 2017, the diabetes prevalence among Han Chinese was 14.7%, the highest among China's ethnic groups, while Tibetans were at 4.3%. But how the high-altitude environment prevents diabetes had not been revealed.
Jain's team has studied how hypoxia, a low oxygen level in the blood, affects human metabolism and health. In earlier work, they found that breathing oxygen-poor air drove mice's blood sugar levels far below normal. That means the mice ate and burned glucose quickly, reducing the risk of diabetes.
The team hypothesized that the glucose had moved elsewhere, but when they tracked it with medical imaging, they could not identify it in any major organ. Yolanda Martí-Mateos, the paper's first author, said, "When we gave sugar to hypoxic mice, it disappeared from the bloodstream immediately," and added, "We examined the muscles, brain, liver, and more, but no organ could explain this phenomenon."
Using a different imaging technique, the researchers discovered that red blood cells were absorbing and consuming glucose. In fact, when mice were raised under hypoxic conditions, not only did red blood cell production rise sharply, those cells also took up more glucose than red blood cells generated under normal oxygen conditions.
◇ Opening a new path for diabetes treatment
Red blood cells' glucose uptake was essential for adapting to low oxygen. The team found that when oxygen becomes scarce, red blood cells absorb glucose and generate molecules that help release oxygen to body tissues.
The findings could energize diabetes treatment. The researchers learned that the benefits mice gained while adapting to chronic hypoxia persisted for months even after oxygen levels returned to normal. Temporarily providing the human body with a low-oxygen environment could help treat diabetes.
Jain said, "Red blood cells serve as a hidden reservoir in glucose metabolism," adding, "This discovery could open a completely new way of thinking about blood sugar control." The team has already demonstrated that potential in earlier work.
In a paper released last year in the international journal Cell, the Gladstone Institutes said that a drug called HypoxyStat, which induces a low-oxygen environment in the body, produced a breakthrough effect in treating the rare disorder Leigh syndrome. HypoxyStat is a pill that makes hemoglobin in red blood cells hold onto oxygen more tightly, blocking oxygen delivery.
Leigh syndrome is an inherited neurodegenerative disease that appears when mitochondria are damaged. Mitochondria produce energy using oxygen. When this process is impaired, oxygen accumulates and instead damages cells. When HypoxyStat was given to mice with Leigh syndrome, oxygen levels fell, lifespan more than tripled even in the late stage of disease, and brain damage and muscle weakness recovered.
The researchers said HypoxyStat also worked better than existing therapies in diabetic mice. Angelo D'Alessandro, a co-author and professor at the University of Colorado School of Medicine, said, "This is the first time HypoxyStat has been used to treat a condition other than a mitochondrial disease," adding, "It opens the way to a fundamentally different approach to diabetes treatment."
◇ Genetic legacy left by Neanderthals
Tibetans adapted to high altitudes thanks to cousins of modern humans who went extinct. A team at the University of California, Berkeley, reported in Nature in 2014 that Tibetans inherited a gene from Denisovans that can regulate oxygen in the blood, allowing them to live at high altitudes. Denisovans are an archaic human whose bones were first found in 2008 in the Denisova Cave in Siberia.
When Homo sapiens migrated, other humans had already settled in Eurasia. They were Neanderthals and Denisovans, cousins of the now-extinct humans. Both are humans of the genus Homo, like Homo sapiens. Neanderthals left Africa and settled in Eurasia 400,000 years ago. Denisovans are thought to have split from Neanderthals 350,000 years ago and spread across Asia.
The UC Berkeley team said that comparing 40 Tibetans and 40 Han Chinese showed that Tibetans carry a specialized variant called EPAS1 that regulates hemoglobin production. The researchers explained that this gene sharply reduces hemoglobin and red blood cell production, preventing hypoxia that commonly occurs above 4,000 meters.
Scientists have recently been finding one legacy after another from Neanderthals and Denisovans in the genomes of modern humans. Svante Pääbo of Germany's Max Planck Institute for Evolutionary Anthropology, winner of the 2022 Nobel Prize in physiology or medicine, showed that Asians and Europeans all carry up to 4% Neanderthal DNA. Modern human genomes also contain material from Denisovans. Today, Filipinos, Papuans in Papua New Guinea, and Australia's Indigenous peoples have up to 6% of their genes matching Denisovans.
Genes passed down from extinct humans have helped people today overcome disease and harsh environments. Pääbo found that genes left by Neanderthals helped overcome COVID-19. In 2021, he reported in the Proceedings of the National Academy of Sciences (PNAS) that "three genes inherited from Neanderthals reduce the risk of severe COVID by 22%." The day is approaching when the genetic legacy left by our cousins evolves into new medicines.
References
Cell Metabolism (2026), DOI: https://doi.org/10.1016/j.cmet.2026.01.019
Cell (2025), DOI: https://doi.org/10.1016/j.cell.2025.01.029
PNAS (2021), DOI: https://doi.org/10.1073/pnas.2026309118
JAMA (2017), DOI: https://doi.org/10.1001/jama.2017.7596
Nature (2014), DOI: https://doi.org/10.1038/nature13408