New research has found that exercise can counter diabetes damage by activating a natural system people have which can grow new blood vessels after the existing ones get destroyed by said disease.
The Centers for Disease and Prevention (CDC) shares that one in every 10 Americans have diabetes. According to the Vascular Biology Center at the Medical College of Georgia, diabetes damages existing blood vessels, hindering people’s innate ability – which is called angiogenesis – to grow new ones when faced with a new disease or an injury.
But with this new research, there’s first evidence that when faced with diabetes, just one 45-minute session of moderate intensity exercise enables more exosomes, which are ‘sub-microscopic packages filled with biologically active cargo,’ to deliver more protein directly to the cells, where angiogenesis can be set into motion.
Dr. Tohru Fukai, MCG vascular biologist and cardiologist, says, “Not unlike the most sophisticated and efficient delivery services we have all come to rely upon, particularly during the pandemic, what exosomes carry depends on where they come from and where they are headed,”
Although he and his co-author, Dr. Masuko Ushio-Fukai, are yet to be certain of the origin of these helpful exosomes, what is clear is that one place they do deliver to is to the endothelial cells, which line the blood vessels and are essential to new growth.
During the study, they tested both animal models of type 2 diabetes, as well as a handful of “healthy” 50-year-olds. The mice were made to do two weeks of volunteer running on a wheel, while the humans were made to do one cardio session. Both groups showed increased levels of ATP7A in the exosomes that attached to endothelial cells.
At that point in the trial, the scientists noted that the activity didn’t show significant impact on the weight of the mice, but it did increase a marker of endothelial function and factors such as vascular endothelial growth factor, which is needed for angiogenesis.
Moreover, the exercise increased the amount of the natural and powerful antioxidant extracellular superoxide dismutase, or SOD3. But according to Ushio-Fukai, the heavier payload of ATP7A, known to deliver the essential mineral copper to the cells, is the key to making good use of the SOD3 present in the system.
SOD3 happens to be an important natural antioxidant that’s produced by vascular smooth muscle cells within the walls of blood vessels, and also skeletal muscle cells. These help us maintain healthy levels of reactive oxygen species, or ROS. ROS is also a natural byproduct of our oxygen use which is important to cell signal, enabling a variety of functions. But, with diabetes, the high blood sugar levels result in high ROS levels that end up hindering the important normal functions.
The scientists have shown that ATP7A levels are lessened in diabetes. Now, they also have some new evidence that ‘exosomes circulating in the plasma of sedentary animal models of type 2 diabetes actually impair angiogenesis when placed in a dish with human endothelial cells, as well as in an animal model of wound healing.’
Already under study as drug-delivery mechanisms, the scientists also suggest that synthetic exosomes could one day work as “exercise mimetic,” which could improve a patient’s ability to grow new blood vessels when diabetes has damaged their innate ability. As a matter of fact, the study authors have already generated exosomes where SOD3 is ‘over-expressed and found improved angiogenesis and healing in a mouse model of diabetes.’
Ushio-Fukai explains that the way it’s supposed to work is that the SOD3 is naturally silenced in endothelia cells so they need to get it from other cells, which also calls for the importance of exosome delivery. Fukai also shares that the SOD3 must also ‘bind to the endothelial cells at its ‘natural spot’ called the heparin-binding domain, and the copper transporter ATP7A must be present to enable SOD3 to be active there.’ Furthermore, Fukai shares that both the ATP7A and the binding site are vital for this. They further note that when they removed the binding site from the endothelial cells, which is something that can happen in nature, they saw that the benefits were lost.
Once the SOD3 is present and active, it converts the ROS superoxide into hydrogen peroxide, or H2O2, which is another signaling ROS that helps support normal endothelial cell function. The Fukais have also reported that in human endothelia cells, when over-expressing SOD3, it promotes angiogenesis by increasing the H2O2.
There is also a copper connection, as it runs throughout this process as endothelial cells regularly use tons of copper, as well as ATP7A, which is known to move the essential mineral that we eat in foods such as whole grains and nuts, is also dependent on copper itself.
Physical exercise, such as walking on a treadmill or running, clues the muscles to contract, which is turn prods the release of exosomes into the blood stream.
During Fukai’s postdoc in the Emory University Section of Cardiology, he was also part of the research group that was first to show how exercise increases SOD3 activity, while it decreased with age and with other diseased states such as hypertension and diabetes.
You can see the study published in the Journal of the Federation of American Societies for Experimental Biology.
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