For many years, scientists noticed an interesting pattern among people who live in mountainous regions.
Communities that live high above sea level, where the air contains less oxygen, appear to develop diabetes less often than people who live closer to sea level.
This observation was reported in several population studies, but the reason behind it remained a mystery.
Researchers knew that something about low oxygen environments seemed to influence the body’s metabolism, yet they could not explain how it worked.
Now scientists at the Gladstone Institutes believe they have found the answer. In a study published in the scientific journal Cell Metabolism, the research team discovered that red blood cells behave very differently when oxygen levels are low.
Under these conditions, the cells begin absorbing large amounts of glucose, the main type of sugar circulating in the bloodstream. In simple terms, the red blood cells start acting like tiny sponges that soak up excess sugar.
Glucose is a key source of energy for the body. After we eat food, especially foods rich in carbohydrates, glucose enters the bloodstream. The hormone insulin helps move this sugar into cells where it can be used for energy.
In people with diabetes, this process does not work properly, causing glucose levels in the blood to remain too high. Over time, high blood sugar can damage blood vessels and organs, leading to serious complications such as heart disease, kidney failure, and nerve damage.
Because of this, scientists have long searched for ways to reduce blood sugar levels more effectively. The new study suggests that the body may already have a natural mechanism for lowering glucose under certain environmental conditions.
The research was led by Dr. Isha Jain, a Gladstone Investigator, a core investigator at the Arc Institute, and a professor of biochemistry at the University of California, San Francisco. Her laboratory focuses on understanding how low oxygen conditions—known scientifically as hypoxia—affect metabolism in the body.
In earlier experiments, Jain’s team observed something unusual. When mice were placed in environments with reduced oxygen, their blood sugar levels dropped quickly. After eating, the animals cleared glucose from their blood much faster than normal. This kind of response is usually associated with better control of blood sugar and lower risk of diabetes.
At first, the researchers assumed that common organs such as the liver, muscles, or brain must be responsible for using the extra glucose. These organs normally consume a large portion of the body’s energy. However, when the scientists carefully measured glucose use in these tissues, they found that none of them could explain the dramatic drop in blood sugar.
This puzzling result led the researchers to look for another explanation. Using a different type of imaging technology, they eventually discovered that red blood cells were responsible for absorbing much of the glucose.
Red blood cells are best known for their role in carrying oxygen through the body. They pick up oxygen in the lungs and deliver it to tissues and organs. Traditionally, scientists believed these cells played only a limited role in metabolism. The new research shows that they may be far more active than previously thought.
The study found that when oxygen levels fall, the body produces more red blood cells. At the same time, each individual red blood cell begins using more glucose than usual. Together, these changes allow the cells to remove large amounts of sugar from the bloodstream.
The research team also worked with experts in red blood cell biology from the University of Colorado Anschutz Medical Campus and the University of Maryland to understand how this process works at the molecular level.
They discovered that red blood cells use glucose to produce a special molecule that helps release oxygen more efficiently to tissues. This process becomes especially important when oxygen is scarce, such as at high altitudes. In this way, the cells help the body adapt to low oxygen while also lowering blood sugar.
The scientists were surprised by how large the effect was. In low oxygen environments, red blood cells accounted for a significant portion of the body’s total glucose consumption. This means they play a much bigger role in regulating blood sugar than researchers had previously recognized.
The study also explored whether this discovery could lead to new treatments for diabetes. The research team tested a drug called HypoxyStat, which was developed in Jain’s laboratory.
The drug mimics some of the effects of low oxygen exposure by causing hemoglobin in red blood cells to hold onto oxygen more tightly. As a result, tissues receive slightly less oxygen, triggering metabolic changes similar to those seen at high altitude.
When the researchers tested HypoxyStat in mice with diabetes, the results were striking. The drug completely reversed high blood sugar levels in the animals and performed better than several existing diabetes treatments.
Interestingly, the metabolic benefits of low oxygen exposure continued for weeks or even months after the mice returned to normal oxygen levels. This suggests that the body may undergo longer-lasting changes when adapting to hypoxia.
The findings could also have implications beyond diabetes. Scientists believe the mechanism may be important in other situations where oxygen levels change, such as intense exercise or severe injuries that affect blood circulation.
When carefully reviewing the study findings, the research provides a new perspective on how the body regulates blood sugar. Instead of focusing only on organs like the liver and muscles, scientists may need to consider the role of red blood cells in controlling glucose levels.
The discovery suggests that red blood cells act as a previously overlooked system for removing sugar from the bloodstream during low oxygen conditions.
However, the research was conducted mainly in animal models, so more studies will be needed to confirm whether the same process works in humans. Clinical trials will also be necessary to determine whether drugs that mimic hypoxia, such as HypoxyStat, can safely treat diabetes in people.
Even so, the study represents an important step forward in understanding metabolism and the body’s response to oxygen levels. It also shows how environmental conditions, such as living at high altitude, can influence disease risk in ways scientists are only beginning to understand.
If you care about diabetes, please read studies about 5 vitamins that may prevent complication in diabetes, and how to manage high blood pressure and diabetes with healthy foods.
For more health information, please see recent studies about vitamin D and type2 diabetes, and to people with type 2 diabetes, some fruits are better than others.
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