• New evidence of how exercise can counter

    From ScienceDaily@1:317/3 to All on Tuesday, April 26, 2022 22:30:44
    New evidence of how exercise can counter diabetes damage

    Date:
    April 26, 2022
    Source:
    Medical College of Georgia at Augusta University
    Summary:
    One way exercise can counter the damage of diabetes is by enabling
    activation of a natural system we have to grow new blood vessels
    when existing ones are ravaged by this disease.



    FULL STORY ==========================================================================
    One way exercise can counter the damage of diabetes is by enabling
    activation of a natural system we have to grow new blood vessels when
    existing ones are ravaged by this disease, scientists report.


    ========================================================================== Angiogenesis is the ability to form new blood vessels, and diabetes
    not only damages existing blood vessels, it hinders this innate ability
    to grow new ones in the face of disease and injury, say experts at the
    Vascular Biology Center at the Medical College of Georgia.

    Endothelial cells line our blood vessels and are essential to that new
    blood vessel growth.

    Now the MCG scientists have the first evidence that in the face of
    diabetes, even one 45-minute session of moderate intensity exercise
    enables 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.

    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, says
    Dr. Tohru Fukai, MCG vascular biologist and cardiologist.

    While he and co-corresponding author MCG vascular biologist Dr. Masuko
    Ushio- Fukai are not yet certain of the origin of these helpful exosomes,
    it's clear that one place they deliver is to endothelial cells,
    Fukai says.



    ==========================================================================
    In both an animal model of type 2 diabetes and a handful of healthy 50- something-year-olds, two weeks of volunteer running on a wheel for the
    mice and that one cardio session for the humans increased levels of
    ATP7A in the exosomes that attached to endothelial cells.

    At that point, the activity did not significantly impact the weight
    of the mice, the scientists note, but it did also increase a marker of endothelial function and factors like, vascular endothelial growth factor, needed for angiogenesis.

    Exercise also increased the amount of the powerful, natural antioxidant extracellular superoxide dismutase, or SOD3, but it's the heavier
    payload of ATP7A, which is also known to deliver the essential mineral
    copper to cells, that is key to making good use of the SOD3 present, Ushio-Fukai says.

    SOD3, is an important natural antioxidant produced by vascular smooth
    muscle cells in the walls of blood vessels as well as skeletal muscle
    cells, which helps us maintain healthy levels of reactive oxygen species,
    or ROS. ROS is a natural byproduct of our use of oxygen that is an
    important cell signal, enabling a variety of functions. But in diabetes,
    high blood sugar levels result in high ROS levels that instead hinder
    important normal functions.

    The Fukais have shown that ATP7A levels are reduced in diabetes. They
    also now have some of the first 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.



    ==========================================================================
    The scientists suggest that synthetic exosomes, already under study as
    drug- delivery mechanisms, could one day work as an "exercise mimetic"
    to improve patients' ability to grow new blood vessels when diabetes
    has damaged their innate ability.

    In fact, they have already generated exosomes in which SOD3 is
    overexpressed and found improved angiogenesis and healing in a mouse
    model of diabetes.

    The way it's supposed to work is SOD3 is naturally silenced in endothelial cells, so they must get it from other cells, notes Ushio-Fukai, hence the importance of exosome delivery. SOD3 must then bind to 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,
    Fukai says. Both ATP7A and the binding site are key, Fukai notes. For
    example, when they removed the binding site from the endothelial cells,
    which can happen in nature, the benefits were lost.

    Once on the scene and active, SOD3 converts the ROS superoxide into
    hydrogen peroxide, or H2O2, another signaling ROS that helps support
    normal endothelial cell function. The Fukais have reported that in
    human endothelial cells, overexpressing SOD3 promotes angiogenesis by increasing H2O2.

    A copper connection also runs throughout this process as endothelial
    cells regularly use a lot of copper, and ATP7A, known to transport the essential mineral that we consume in foods like nuts and whole grains,
    is dependent on copper itself.

    Physical exercise, like running or walking on treadmill, prompts muscles
    to contract which in turn prompts release of exosomes into the blood.

    When Fukai was a postdoc in the Emory University Section of Cardiology he
    was part of the research group that was the first to show that exercise increases SOD3 activity. SOD3 levels decrease with age and with some
    disease states like diabetes and hypertension.

    Exosomes are being studied as biomarkers for a wide range of diseases
    like cancer and diabetes as well as precise treatment delivery tools. For example, exosomes produced by a cancer cell will hone right back to a
    cancer cell.

    About 1 in 10 Americans have diabetes, according to the Centers for
    Disease Control and Prevention.


    ========================================================================== Story Source: Materials provided by Medical_College_of_Georgia_at_Augusta_University.

    Original written by Toni Baker. Note: Content may be edited for style
    and length.


    ========================================================================== 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 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220426101747.htm

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