Researchers at Gladstone Institutes say a new mechanism helps explain why people living at high altitude seem less likely to develop diabetes: red blood cells grab extra sugar when oxygen is low, acting like a temporary sponge and lowering blood glucose. Laboratory work in mice showed those cells soak up more glucose under hypoxic conditions and that a drug mimicking the effect can reverse high blood sugar in diabetic animals. The team notes limits to the work and calls for broader testing across ages, sexes, and genetic backgrounds.
The headline finding is straightforward and surprising: red blood cells do more than shuttle oxygen. In thin air, these cells change gears and take on a metabolic task, pulling glucose from the bloodstream in amounts researchers had not expected. That shift appears to reduce the glucose that would otherwise linger in circulation, which helps explain lower diabetes rates in mountain communities.
The discovery started with a puzzle. Mice put in low-oxygen conditions cleared sugar from their blood almost instantly after a meal, a pattern normally associated with protection from diabetes. Scientists searched the usual organs for an explanation and came up empty, which pushed them to try different imaging and metabolic approaches. “We looked at muscle, brain, liver — all the usual suspects — but nothing in these organs could explain what was happening,” said Yolanda Martí-Mateos, a postdoctoral scholar in Jain’s lab and the study’s first author.
When they turned to red blood cells, the answer appeared. Under hypoxia, mice produced more red blood cells and each cell absorbed far more glucose than under normal oxygen conditions. In other words, the circulating cells themselves became an overlooked glucose reservoir, lowering blood sugar by hoarding sugar inside cells designed for oxygen transport. This flips a common assumption about where glucose can be stored and used in the body.
Senior author Isha Jain framed the shift as revealing a hidden side of metabolism. “Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” said senior author Isha Jain, a Gladstone investigator and professor of biochemistry at UC San Francisco, in the press release. That idea opens room for new strategies to influence blood sugar without directly targeting insulin or typical metabolic organs.
The team pushed the concept toward application by designing a compound called HypoxyStat that imitates the high-altitude trigger. In lab tests the drug reversed high blood sugar in diabetic mice, offering a proof of principle that the mechanism can be harnessed pharmaceutically. Those results are early, but they hint at alternatives to existing diabetes treatments that work through different pathways.
The study has clear boundaries. Researchers used a particular mouse strain that is sensitive to changes in blood sugar, and they limited experiments to young male animals to reduce variability. Because age and sex both influence red blood cell production and metabolic responses, the authors warn that follow-up work must test other strains, females, and older subjects to see how broadly the findings apply.
“This is just the beginning,” Jain said. There’s a lot left to test in other models and in human studies before any treatment ideas move to the clinic. “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.”
Beyond the lab bench, the results help explain epidemiological patterns seen in people who live at higher elevations. Large population studies have found lower rates of diabetes among residents living between roughly 1,500 and 3,500 meters, even after accounting for diet, age, and ethnicity. The new mechanistic insight gives a biologically plausible reason why altitude might alter diabetes risk, and it points researchers to a less obvious player in glucose control: the red blood cell.
