- A study suggests that under low-oxygen conditions, red blood cells can act as a ‘glucose sink’ and absorb significantly more glucose from the bloodstream than previously recognized.
- Both the number of red blood cells and their glucose uptake increased in low-oxygen conditions, amplifying their overall impact on whole-body glucose metabolism.
- Exposure to hypoxia, such as at high altitudes, improved glucose tolerance in mice and reversed high blood sugar levels, suggesting a potential new therapeutic strategy for diabetes.
It is a comprehensive, daily effort that combines monitoring, lifestyle adjustments, and when necessary, medication.
Physical activity can be a useful strategy to manage blood glucose levels. It works by increasing insulin sensitivity, allowing cells to use available insulin to take up glucose in the bloodstream during and after activity.
Similarly, some diabetes medications help to manage blood glucose levels by improving insulin sensitivity, or increasing insulin production.
Now, research is suggesting that another component present in the blood my also play a role in regulating blood sugar levels, by acting as a “glucose sponge” and soaking up sugar from the bloodstream.
A recent study, published in Cell Metabolism, reports that red blood cells can dramatically increase their uptake of glucose in low-oxygen environments, which may offer a potential explanation for the reduced diabetes risk seen at high elevations.
The biological mechanism behind this protective effect was unclear, but the study led by scientists from the Gladstone Institutes may offer an answer.
Exploring this observation further, the researchers identified that when oxygen is scarce, red blood cells adapt by pulling more glucose out of the bloodstream.
This “glucose sink” effect not only fuels the cells’ own energy needs, but also reduces circulating blood sugar levels.
Senior author of the study, Isha Jain, PhD, an associate investigator at Gladstone Institutes, and an associate [rofessor at UCSF highlighted the findings from the study to Medical News Today.
“We identified two mechanisms. First, red blood cell numbers increase in chronic hypoxia, thereby increasing total glucose-consuming capacity. Second, individual RBCs from hypoxic environments take up more glucose per cell due to higher glucose transporter type 1 (GLUT1) transporter levels,” said Jain.
“We identified two mechanisms. First, red blood cell numbers increase in chronic hypoxia, thereby increasing total glucose-consuming capacity. Second, individual RBCs from hypoxic environments take up more glucose per cell due to higher glucose transporter type 1 (GLUT1) transporter levels.”
– Isha Jain, PhD
“We also found that hypoxic red blood cells metabolize glucose faster to produce 2,3-diphosphoglycerate (2,3-DPG), a molecule that helps hemoglobin release oxygen to tissues,” she added.
“The mechanism involves deoxygenated hemoglobin displacing glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the cell membrane, removing a brake on glycolysis,” the researcher detailed.
In the study, the researchers exposed mice to conditions that mimicked high-altitude hypoxia. This describes when body tissues are deprived of adequate oxygen.
The team observed that blood glucose levels dropped rapidly, better glucose tolerance developed, and traditional glucose-consuming tissues, such as muscles, the brain, and the liver, did not fully explain where the sugar was going.
Using advanced imaging techniques, the researchers found that red blood cells were absorbing a significant amount of sugar from the blood circulation.
Under the low-oxygen conditions, the mice were not only producing more red blood cells, but each cell was absorbing more glucose than under normal oxygen levels.
The researchers propose that red blood cells support oxygen delivery while reducing blood sugar, by shunting glucose into pathways that help generate molecules necessary for efficient oxygen release to tissues.
“While we showed that hypoxia reversed hyperglycemia in mouse diabetes models, we do not know how these findings translate to human physiology or what duration and intensity of exposure would be needed,” Jain said.
“The epidemiological associations are intriguing and consistent with our findings, but many factors differ between high and low altitude populations beyond oxygen levels, including diet, activity patterns, genetics, healthcare access,” she told us.
“For people with diabetes considering high-altitude activities, safety should remain the primary consideration,” added the study author.
However, this potentially beneficial effect may not be suitable for all individuals living with diabetes.
People living with type 1 diabetes are more likely to experience hypoglycemia, or low blood sugar, than those with type 2 diabetes. Previous research has highlighted that higher altitudes may increase the risk of hypoglycemia in those with type 1 diabetes, particularly when exercising.
This is likely due to a combination of factors, such as the role of red blood cells at higher altitudes, as well as a loss of a counterregulatory hormonal response in those living with type 1 diabetes.
Jain noted that the study examined chronic adaptation to hypoxia in mice without diabetes medications, so it is not yet known how it could affect those living with type 1 diabetes.
“People with type 1 diabetes on insulin therapy face a completely different physiological context. People with diabetes planning high-altitude activities should work closely with their healthcare providers,” she told us.
In addition to understanding altitude physiology, the study suggests potential therapeutic avenues for managing blood sugar levels.
The scientists tested a small molecule, called HypoxyStat, which was recently developed in Jain’s lab. This drug mimics the effects of low oxygen by altering how hemoglobin binds oxygen. By grabbing onto oxygen more tightly, it prevents it from reaching tissues.
In the study, HypoxyStat was able to reverse hyperglycemia, or high blood sugar levels, in mouse models of diabetes, working even better than some existing medications.
When asked which populations may benefit the most from these findings, Jain commented:
“We would need carefully controlled human studies before recommending altitude-based or hypoxia-based therapies for specific patient populations, but the mechanisms we identified could someday inspire therapeutic strategies that do not require altitude exposure.”
“We showed that HypoxyStat, a small molecule our lab developed, reversed hyperglycemia in diabetic mice by mimicking hypoxia effects. This suggests potential pharmacological approaches without the risks of actual hypoxia exposure,” she explained.
Although these findings are still early and in mouse models, they raise intriguing questions about the body’s response to oxygen levels and whether diabetes treatments could one day harness these mechanisms in humans.
“We are not able to suggest that this work supports specific interventions like hypoxic training or hypobaric chambers at this stage. Those would require rigorous clinical trials to establish safety and efficacy,” Jain said.
“Our work provides a previously unrecognized mechanism linking oxygen levels to glucose homeostasis through red blood cells. The more immediate impact might be understanding glucose dynamics in people who already live at altitude or have conditions affecting RBC counts,” noted the researcher.
