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Exercise can help reverse diabetic damage: Research

by Pragati Singh

Exercise can help to mitigate the effects of diabetes by activating a natural system that allows us to build new blood vessels when the illness destroys old ones.

Angiogenesis is the ability to generate new blood vessels, and diabetes not only destroys existing blood vessels but also inhibits this intrinsic potential to develop new ones in the face of sickness and injury, according to specialists from the Medical College of Georgia’s Vascular Biology Center. Endothelial cells line our blood vessels and are critical to the formation of new blood vessels.

In the face of diabetes, the MCG researchers now have the first evidence that even one 45-minute session of moderate intensity exercise allows more exosomes, submicroscopic packages filled with biologically active cargo, to deliver directly to those cells more of the protein, ATP7A, which can set angiogenesis in motion, they report in The FASEB Journal.

What exosomes convey, like the most sophisticated and efficient delivery systems we’ve all come to rely on, depends on where they came from and where they’re going, says Dr. Tohru Fukai, MCG vascular biologist and cardiologist.

While he and co-corresponding author MCG vascular scientist Dr. Masuko Ushio-Fukai aren’t sure where these beneficial exosomes come from, Fukai says one location they go is to endothelial cells.

Two weeks of volunteer jogging on a wheel for mice and one cardio session for people boosted levels of ATP7A in exosomes that adhered to endothelial cells in both animal models of type 2 diabetes and a handful of healthy 50-somethings.

The activity did not significantly affect the weight of the mice at that time, but it did improve a marker of endothelial function and substances like vascular endothelial growth factor, which are required for angiogenesis, according to the researchers.

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Diabetes reduces ATP7A levels, according to the Fukais. They also have some of the first evidence that exosomes circulating in the plasma of sedentary animal models of type 2 diabetes inhibit angiogenesis when put in a dish with human endothelial cells and in an animal model of wound healing.

The researchers believe that synthetic exosomes, which are already being studied as medication delivery systems, might one day be used as a “exercise mimic” to boost patients’ ability to create new blood vessels after diabetes has compromised their intrinsic ability.

In fact, they have previously created exosomes with SOD3 overexpression and discovered better angiogenesis and healing in a diabetic animal model.

SOD3 is normally muted in endothelial cells, therefore they must obtain it from other cells, according to Ushio-Fukai, emphasising the need of exosome delivery. According to Fukai, SOD3 must then attach to endothelial cells at its native site known as the heparin-binding domain, and the copper transporter ATP7A must be present for SOD3 to be active there. Fukai emphasises the importance of ATP7A and the binding location. The advantages were lost, for example, when scientists eliminated the binding site from the endothelial cells, as might happen in nature.

Once activated, SOD3 transforms the ROS superoxide to hydrogen peroxide, or H2O2, another signalling ROS that aids regular endothelial cell activity.

The Fukais discovered that overexpressing SOD3 in human endothelial cells increases angiogenesis by raising H2O2.

Endothelial cells constantly utilise a lot of copper, and ATP7A, which is known to transport the vital mineral that we ingest in foods like nuts and whole grains, is dependent on copper itself.

Exercising, such as jogging or walking on a treadmill, causes muscles to contract, resulting in the release of exosomes into the circulation.

Fukai was a postdoctoral fellow in the Emory University Section of Cardiology and was part of the research team that discovered that exercise boosts SOD3 activity. SOD3 levels decline with age and in some diseases such as diabetes and hypertension.

Exosomes are being investigated as precise medication delivery systems and biomarkers for a variety of illnesses, including diabetes and cancer. For instance, a cancer cell’s exosomes will immediately return to that particular cancer cell.

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