Scientists discover reason why high altitude protects people against diabetes

Living at high altitude appears to protect against diabetes and scientists have finally discovered the reason When oxygen levels drop red blood cells switch into a new metabolic mode and absorb large amounts of glucose from the bloodThis helps the body cope with thin air while also reducing blood sugar levels A drug that recreates this effect reversed diabetes in mice hinting at a powerful new treatment strategyFor years researchers have observed that people who live at high elevations where oxygen is scarce tend to develop diabetes less often than those at sea level Although the trend was well documented the biological explanation behind it was unclearScientists at Gladstone Institutes now say they have identified the reason Their research shows that in low oxygen environments red blood cells begin absorbing large amounts of glucose from the bloodstreamIn effect the cells act like sugar sponges under conditions similar to those found on the worlds tallest mountainsIn findings published in Cell Metabolism the team demonstrated that red blood cells can alter their metabolism when oxygen levels dropThis shift allows the cells to deliver oxygen to tissues more efficiently at high altitude At the same time it lowers circulating blood sugar offering a potential explanation for reduced diabetes riskAccording to senior author Isha Jain PhD a Gladstone Investigator core investigator at Arc Institute and professor of biochemistry at UC San Francisco the study resolves a longstanding question in physiologyRed blood cells represent a hidden compartment of glucose metabolism that has not been appreciated until now This discovery could open up entirely new ways to think about controlling blood sugar Jain saysRed blood cells identified as a glucose sinkJains lab has spent years studying hypoxia the term for reduced oxygen levels in the blood and its effects on metabolism In earlier experiments her team noticed that mice exposed to low oxygen air had dramatically lower blood glucose levelsThe animals rapidly cleared sugar from their bloodstream after eating which is typically linked to lower diabetes risk However when researchers examined major organs to determine where the glucose was being used they found no clear answerWhen we gave sugar to the mice in hypoxia it disappeared from their bloodstream almost instantly says Yolanda MartiMateos PhD a postdoctoral scholar in Jains lab and first author of the new study We looked at muscle brain liver all the usual suspects but nothing in these organs could explain what was happeningUsing a different imaging method the researchers discovered that red blood cells were serving as the missing glucose sink meaning they were taking in and using significant amounts of glucose from circulationThis was unexpected because red blood cells have traditionally been viewed as simple oxygen carriersFollow up experiments in mice confirmed the finding Under low oxygen conditions the animals produced more red blood cells overall and each individual cell absorbed more glucose compared with cells formed under normal oxygen levelsTo uncover the molecular details behind this shift Jains group partnered with Angelo DAlessandro PhD of the University of Colorado Anschutz Medical Campus and Allan Doctor MD from University of Maryland who has long studied red blood cell biologyTheir work showed that when oxygen is limited red blood cells use glucose to generate a molecule that helps release oxygen to tissues This process becomes especially important when oxygen is in short supplyWhat surprised me most was the magnitude of the effect DAlessandro says Red blood cells are usually thought of as passive oxygen carriers Yet we found that they can account for a substantial fraction of wholebody glucose consumption especially under hypoxiaImplications for diabetes treatmentThe researchers also found that the metabolic benefits of prolonged hypoxia lasted for weeks to months after mice were returned to normal oxygen levelsThey then evaluated HypoxyStat a drug recently developed in Jains lab that mimics low oxygen exposure HypoxyStat is taken as a pill and works by causing hemoglobin in red blood cells to bind oxygen more tightly limiting the amount delivered to tissues In mouse models of diabetes the medication completely reversed high blood sugar and outperformed existing treatmentsThis is one of the first use of HypoxyStat beyond mitochondrial disease Jain says It opens the door to thinking about diabetes treatment in a fundamentally different way by recruiting red blood cells as glucose sinksThe findings may also apply beyond diabetes DAlessandro notes potential relevance for exercise physiology and for pathological hypoxia after traumatic injury Trauma remains a leading cause of death among younger people and changes in red blood cell production and metabolism could affect glucose availability and muscle performanceThis is just the beginning Theres 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 Jain saysThis story has been sourced from a third party syndicated feed agencies Midday accepts no responsibility or liability for its dependability trustworthiness reliability and data of the text Midday managementmiddaycom reserves the sole right to alter delete or remove without notice the content in its absolute discretion for any reason whatsoever