Scientists have known for decades that people living at higher altitudes, where oxygen is scarce, have lower rates of diabetes, and it’s a phenomenon that’s not restricted to humans. Tibetan pigs, deer mice, snowfinches, and other animals all have tighter control of their blood sugar at high altitudes as well.
So what’s going on?
According to new research published in Cell Metabolism the answer might be hiding in the blood.
Isha Jain, a cardiovascular scientist at the Gladstone Institutes in San Francisco and an expert on how our bodies use oxygen, learned in previous work that mice experiencing low oxygen levels (hypoxia) had much lower blood glucose levels. “When we gave sugar to the mice in hypoxia, it disappeared from their bloodstream almost instantly,” Yolanda Martí-Mateos, co-author of the latest study, explained in a statement. “We looked at muscle, brain, liver—all the usual suspects—but nothing in these organs could explain what was happening.”
After performing a battery of tests on hypoxic mice, the team discovered that red blood cells were responsible for soaking up the excess glucose. It was a somewhat counterintuitive finding; after all, red blood cells are pretty simple structures. Without nuclei and mitochondria, they’re basically stripped-down vehicles for oxygen-carrying hemoglobin. On the other hand, what they lack in metabolic demands, they make up for in sheer numbers, as the most abundant cell in the body.
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And so, when the mice were exposed to chronic hypoxic conditions two things happened. First, like us, they produced a lot more red blood cells. Second, these new red blood cells were a little different—they were primed to absorb sugar with a lot more glucose transporters on their surface. Taken together, these two factors caused blood glucose to plummet.
While the study found red blood cells were the primary glucose sink in hypoxic conditions, reducing blood sugar was a secondary effect—the red blood cells simply needed more fuel to carry out their job of oxygenating the tissues.
“What surprised me most was the magnitude of the effect,” study co-author Angelo D’Alessandro of the University of Colorado said. “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.”
Going forward, the team hopes to apply these findings to treatments for diabetes, traumatic injuries, and even exercise physiology.
“This is just the beginning,” Jain said. “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.” 
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