New evidence on how exercise fights diabetes damage

Angiogenesis is the ability to form new blood vessels, and diabetes not only damages existing blood vessels, but also hinders this innate ability to grow new blood vessels in the face of disease and injury, according to experts at the Center for Vascular Biology at the Georgia School of Medicine

Endothelial cells line our blood vessels and are essential for the growth of new blood vessels

Now, for the first time, MCG scientists have evidence that even 45 minutes of moderate-intensity exercise in the face of diabetes can cause more exosomes, submicroscopic packages filled with biologically active substances, to deliver directly to these cells Deliver more of the protein, ATP7A, which can initiate angiogenesis, they report in the journal FASEB

MCG's vascular biologist and cardiologist Dr Tohru Fukai said, "Just like the most complex and efficient delivery services we rely on, especially during a pandemic, what exosomes carry depends on where they come from.

While he and co-corresponding author MCG vascular biologist Masuko Ushio-Fukai, Ph.

In animal models of type 2 diabetes and in some healthy people in their 50s, mouse volunteers ran on wheels for two weeks, and human volunteers had levels of ATP7A attached to endothelial cells in exosomes during aerobic exercise.

At this point, the scientists noted, the activity did not significantly affect the weight of the mice, but it also increased markers of endothelial function, as well as factors required for angiogenesis such as vascular endothelial growth factor

Exercise also increases the amount of extracellular superoxide dismutase (SOD3), a powerful, natural antioxidant, but a heavier load on ATP7A, which is also thought to deliver the essential mineral copper to cells, Ushio-Fukai said.

SOD3 is an important natural antioxidant produced by vascular smooth muscle cells and skeletal muscle cells in blood vessel walls, and it helps us maintain healthy levels of reactive oxygen species (ROS)

The Fukui couple found that people with diabetes had lower levels of ATP7A

Scientists believe that synthetic exosomes, already being studied as a drug delivery mechanism, could one day serve as a "mock exercise" to improve a patient's ability to grow new blood vessels when diabetes impairs their innate ability

In fact, they have generated SOD3-overexpressing exosomes and found improvements in angiogenesis and healing in a mouse model of diabetes

Ushio-Fukai pointed out that SOD3 is naturally silenced in endothelial cells, so it must be obtained from other cells, so the delivery of exosomes is important

Once present and activated, SOD3 converts ROS superoxide into hydrogen peroxide, or H2O2, another signaling ROS that helps support normal endothelial cell function

Since endothelial cells often use large amounts of copper, copper connections also run through the process, and ATP7A, the transporter of important minerals we consume from foods like nuts and whole grains, depends on copper itself

Physical exercise, such as running or walking on a treadmill, induces muscle contraction, which in turn induces the release of exosomes into the bloodstream

When Fukai was a postdoc in the Department of Cardiology at Emory University, he was part of the first research group to show that exercise increases SOD3 activity
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SOD3 levels decrease with age and with diseases such as diabetes and high blood pressure
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Exosomes are being studied as biomarkers for a wide range of diseases, such as cancer and diabetes, as well as precision therapy delivery tools
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For example, exosomes produced by cancer cells are honed back into cancer cells
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About 1 in 10 Americans have diabetes, according to the Centers for Disease Control and Prevention
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Journal Reference :

1. Kareem Abdelsaid, Varadarajan Sudhahar, Ryan A.
   Harris, Archita Das, Seock‐Won Youn, Yutao Liu, Maggie McMenamin, Yali Hou, David Fulton, Mark W.
   Hamrick, Yaoliang Tang, Tohru Fukai, Masuko Ushio‐Fukai.
   Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3 .
   The FASEB Journal , 2022; 36 (3) DOI: 10.
   1096/fj.
   202101323R