High-Altitude Living and Diabetes: How Thin Air May Offer Protection

For decades, scientists have observed a curious trend: individuals residing in high-altitude regions like Tibet, Peru, and Nepal exhibit lower rates of diabetes. Now, a new study from the Gladstone Institutes sheds light on the underlying mechanism, revealing a surprising role for red blood cells in regulating blood sugar levels.

Red Blood Cells: More Than Just Oxygen Carriers

Traditionally known for transporting oxygen throughout the body, red blood cells also function as significant glucose absorbers, particularly when oxygen levels are low—a condition known as hypoxia. Researchers discovered that at high altitudes, red blood cells grow a major “glucose sink,” effectively removing glucose from the bloodstream.

How Hypoxia Impacts Glucose Metabolism

The study, published in Cell Metabolism, involved exposing mice to low oxygen conditions. Within days, researchers observed a substantial drop in blood sugar levels, and the mice cleared glucose from their blood at an accelerated rate. Remarkably, this improvement persisted for weeks even after oxygen levels returned to normal.

Interestingly, this glucose removal process doesn’t rely on insulin. In fact, insulin sensitivity actually decreased during hypoxia, indicating that the body employs a different mechanism to regulate blood sugar in low-oxygen environments.

Where Does the Glucose Go?

Initially, scientists hypothesized that muscles or the liver might be responsible for utilizing the excess glucose. However, imaging studies revealed that most internal organs couldn’t account for the significant reduction in blood sugar. The key lies within the red blood cells themselves.

Under hypoxic conditions, red blood cells increase in number and each cell absorbs three times more glucose due to an increase in the glucose carriers GLUT1, and GLUT4. This absorbed glucose is then directed towards the production of 2,3-DPG, a molecule crucial for hemoglobin to efficiently deliver oxygen to tissues. This oxygen-dependent switch accelerates glycolysis—the breakdown of glucose—without the demand for gene activation.

Implications for Diabetes Treatment

The findings have significant implications for the development of new diabetes treatments. In diabetic mice, both hypoxia and red blood cell transfusions were shown to lower blood sugar levels. This suggests that controlling glucose consumption by red blood cells could be a novel therapeutic strategy.

“Red blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now,” says Dr. Isha Jain, senior author of the study. “This discovery could open up entirely new ways to think about controlling blood sugar.”

Gladstone Institutes: Leading the Way in Biomedical Research

The Gladstone Institutes, a leading biomedical research organization, are dedicated to overcoming unsolved diseases. Their research spans a wide range of areas, including cardiovascular disease, genetic diseases, infectious diseases, neurological disease, and data science and biotechnology. Learn more about their work.

Key Takeaways

• People living at high altitudes tend to have lower blood sugar levels and reduced rates of diabetes.
• Red blood cells become major glucose absorbers in low-oxygen (hypoxic) conditions.
• This glucose removal process is independent of insulin.
• The findings suggest a potential new therapeutic approach for diabetes by targeting glucose metabolism in red blood cells.