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 sponges that absorb glucose in low-oxygen conditions. If a low-oxygen environment can be created in the human body, it is expected to treat diabetes. The same approach has previously been used to treat a congenital neurological disease.
Isha Jain of the Gladstone Institutes in the United States and her team said on the 20th in the international journal Cell Metabolism that "red blood cells become sponges that absorb glucose in low-oxygen environments like the world's highest peaks to enhance their ability to deliver oxygen, and as a side effect also lower blood sugar levels."
◇Tibetan diabetes rate is one-third that of Han Chinese
Scientists have long known that people living in high-altitude areas 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 it was 4.3% among Tibetans. But it was not known how the high-altitude environment prevents diabetes.
Jain's team has studied how hypoxia—low oxygen levels in the blood—affects human metabolism and health. In earlier work, they found that breathing oxygen-poor air makes mice's blood sugar levels markedly lower than normal. That means the mice ate and burned glucose quickly, reducing the risk of diabetes.
The team suspected the glucose was moving elsewhere, but when they tracked it with medical imaging, they could not find it in any major organ. Yolanda Martí-Mateos, the first author of the new paper, said, "When we administered sugar to hypoxic mice, it disappeared from the bloodstream immediately," adding, "We examined the muscles, brain, liver and more, but no organ could explain this phenomenon."
Using a different imaging method, the researchers found 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 increase sharply, but the cells also absorbed more glucose than red blood cells generated under normal oxygen conditions.
◇Opening a new path for diabetes treatment
Red blood cells' absorption of glucose was essential for adapting to low-oxygen environments. 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 be a turning point for diabetes treatment. The team discovered that benefits arising as mice adapt to chronic hypoxia can last for months even after oxygen levels return to normal. Temporarily providing a low-oxygen environment to the human body 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 research.
The Gladstone Institutes said in a paper released last year in the international journal Cell that it achieved a breakthrough in treating the rare disorder Leigh syndrome by inducing a low-oxygen environment in the human body with a drug called HypoxyStat. HypoxyStat is a pill that blocks oxygen delivery by making hemoglobin in red blood cells hold on to oxygen more tightly.
Leigh syndrome is a hereditary 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, and even in the late stage of the disease, lifespan more than tripled and brain damage and muscle weakness recovered.
The team said HypoxyStat also outperformed existing treatments in mice with diabetes. Angelo D'Alessandro, a co-author of the paper and a professor at the University of Colorado School of Medicine, said, "This is the first use of HypoxyStat to treat a disease other than a mitochondrial disorder," adding, "It opens a way to approach diabetes treatment in a fundamentally different way."
◇A genetic legacy left by Neanderthals
Tibetans adapted to high altitudes thanks to cousins of modern humans who went extinct. Researchers 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 group first identified from bones found in 2008 in the Denisova Cave in Siberia.
There were human groups that settled in Eurasia before Homo sapiens migrated there: Neanderthals and Denisovans, cousins of the now-extinct human lineages. 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 through Asia.
The UC Berkeley team said that after comparing 40 Tibetans and 40 Han Chinese, they confirmed that Tibetan genomes contain a special variant called EPAS1 that regulates hemoglobin production. The researchers explained that this gene greatly reduces hemoglobin and red blood cell production, preventing hypoxia that commonly occurs above 4,000 meters.
Scientists have recently been finding Neanderthal and Denisovan legacies in modern human DNA. Svante Pääbo of Germany's Max Planck Institute for Evolutionary Anthropology, winner of the 2022 Nobel Prize in physiology or medicine, found that Asians and Europeans each carry up to 4% Neanderthal DNA. Modern human genomes also contain material from Denisovans. Today, people in the Philippines and Papua New Guinea and Aboriginal Australians have up to 6% of their DNA matching Denisovans.
Genes passed down from extinct humans have helped modern humans overcome disease and harsh environments. Pääbo found that genes left by Neanderthals helped overcome COVID-19. In 2021, Pääbo 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 will yield new drugs.
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