Red blood cells carry oxygen. Everyone knows this. But Jain et al. (Cell Metabolism, 2026) found they also carry glucose — and this hidden function explains a decades-old epidemiological puzzle.
People living at high altitude have lower rates of diabetes. The observation is robust and old. The mechanism was unknown.
Jain's team put mice in low-oxygen conditions and watched glucose disappear from their bloodstream almost instantly. Something was absorbing it — but PET/CT imaging of the major organs couldn't account for all the missing glucose. The sink was somewhere the imaging wasn't looking.
It was in the blood itself. Red blood cells under hypoxia switch metabolic mode. Deoxyhemoglobin — the form that has already released its oxygen — displaces GAPDH from band 3 on the red blood cell membrane. This unlocks glycolytic flux. The cells absorb glucose and burn it to produce 2,3-DPG, a molecule that helps hemoglobin release oxygen to tissues more efficiently. The glucose absorption is a side effect of oxygen optimization.
In chronic hypoxia, newly synthesized red blood cells show roughly threefold increases in GLUT1, the glucose transporter. The cells are physically rebuilt for higher glucose uptake. The effect persists for weeks after returning to normal oxygen — because red blood cells live 120 days, and the remodeled ones stay in circulation.
The structural insight: red blood cells were invisible to metabolic research because they were classified as transport, not metabolism. They carry things. They don't consume things. Except they do, substantially, under conditions that change their hemoglobin's conformational state.
A drug called HypoxyStat reverses the logic. It makes hemoglobin grip oxygen more tightly, mimicking the deoxy state, which triggers the glucose-sink cascade at sea level. In diabetic mice, it completely reversed high blood sugar — working better than existing medications. The therapy doesn't target insulin, or the pancreas, or the liver. It targets oxygen binding in the most abundant cell in the body.
“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” Jain said.
The hidden compartment. Not hidden because it was small or rare — red blood cells are 70% of all human cells — but because the classification system put them in the wrong category. The metabolic textbook had a chapter on glucose uptake in muscle, liver, fat, brain. Red blood cells weren't in the chapter. The compartment was hidden by the table of contents.
This is the measurement-order problem again. You find glucose sinks by imaging organs. Red blood cells aren't organs. They're distributed through the entire vascular system, present everywhere the imaging looks but belonging to no single location. The PET/CT saw them in every scan and attributed their signal to the tissues surrounding them. The sink was hiding inside the measurement itself.
Jain et al., "Red blood cells serve as a primary glucose sink to improve glucose tolerance at altitude," Cell Metabolism (2026).