Exercise and the Receptor for Advanced Glycation End Products (RAGE)

Clinical Trial ID: NCT03534687

Description

This study examines the effects of 12-weeks of aerobic exercise training on the mechanisms driving RAGE-mediated inflammation in type 2 diabetic humans.

Activation of RAGE (receptor of advanced glycation endproducts (AGEs)), via binding of AGEs and other ligands, modulates the development and progression of diabetic complications through persistent and cyclic activation of nuclear factor-kappa beta. Targeting RAGE directly as a therapeutic strategy has largely been unsuccessful. However, RAGE signaling can be interrupted, in vivo, by ADAM10 (a disintegrin and metalloproteinase 10) directed proteolytic cleavage of the RAGE ectodomain, and thus creating a soluble isoform of RAGE (sRAGE) that is released from the cell and appears into the circulation. Maintaining high levels of circulating sRAGE is advantageous as sRAGE will sequester RAGE ligands and prevent RAGE cell signaling. Although the exact mechanisms of ADAM10 mediated RAGE release remain undefined, calcium related and other signaling (SIRT1) impact ADAM10. Aerobic exercise presents a unique model for mechanistic study of RAGE release as muscle contraction induces robust calcium signaling, activates SIRT1, and provides stimuli for tissue remodeling and resolution of the metabolic profile that drives inflammation.


Criteria

Inclusion Criteria: - Age 40-75 y - Type 2 diabetes - Overweight or obese (BMI 26-44 kg/m2) - Fluency in English (written and verbal) Exclusion Criteria: - Age <40 or >75 y - BMI <26 or >44 kg/m2 - Existing cardiovascular, cerebrovascular, renal, or hematological disease, or cancer - Current use of tobacco - Pregnant or lactating - Medications that may interfere with study outcomes

  • Start Date

    2018-12-20

  • Last Updated

    2019-01-18

  • Sponsor

    National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  • Condition Name

    Diabetes Mellitus, Type 2

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