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    The chaperone balance hypothesis: The importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management

    230106_230106.pdf (1.382Mb)
    Access Status
    Open access
    Authors
    Krause, M.
    Heck, T.
    Bittencourt, A.
    Scomazzon, S.
    Newsholme, Philip
    Curi, R.
    Homem De Bittencourt, P.
    Date
    2015
    Type
    Journal Article
    
    Metadata
    Show full item record
    Citation
    Krause, M. and Heck, T. and Bittencourt, A. and Scomazzon, S. and Newsholme, P. and Curi, R. and Homem De Bittencourt, P. 2015. The chaperone balance hypothesis: The importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Mediators of Inflammation. Article ID 249205, 12 pages.
    Source Title
    Mediators of Inflammation
    DOI
    10.1155/2015/249205
    ISSN
    0962-9351
    School
    School of Biomedical Sciences
    Remarks

    This open access article is distributed under the Creative Commons license http://creativecommons.org/licenses/by/3.0/

    URI
    http://hdl.handle.net/20.500.11937/5082
    Collection
    • Curtin Research Publications
    Abstract

    Recent evidence shows divergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For example, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways. Increased eHSP70 is associated with inflammatory and oxidative stress conditions, whereas decreased iHSP70 levels are related to insulin resistance in skeletal muscle. Serum eHSP70 concentrations are positively correlated with markers of inflammation, such as C-reactive protein, monocyte count, and TNF-a, while strategies to enhance iHSP70 (e.g., heat treatment, chemical HSP70 inducers or coinducers, and physical exercise) are capable of reducing the inflammatory profile and the insulin resistance state. Here, we present recent findings suggesting that imbalances in the HSP70 status, described by the [eHSP70]/[iHSP70] ratio, may be determinant to trigger a chronic proinflammatory state that leads to insulin resistance and T2DM development. This led us to hypothesize that changes in this ratio value could be used as a biomarker for the management of the inflammatory response in insulin resistance and diabetes.

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