Over the past decade, work from our research group has demonstrated that over-expression or activation of the chaperone protein heat shock protein 72 (HSP72; the inducible form of the 70kDa family of heat shock proteins) in skeletal muscle reduces obesity-induced insulin resistance (for review see). These findings led to the development of the small molecule activator of HSP72, namely BGP-15 which, in pre-clinical studies, has proven to be effective in the treatment of several diseases including type 2 diabetes, atrial fibrillation and Duchenne Muscular Dystrophy. While we originally ascribed the mechanism of action of HSP72 activation to preventing inflammation and endoplasmic reticulum (ER) stress, we have recently shown that HSP72 is both necessary and sufficient to maintain mitochondrial structure and function in the context of obesity and insulin resistance. These recent results are most significant as they suggest that HSP72 may be a therapeutic target for not only T2D, but for conditions in which mitochondrial function is impaired. Recent work on the role of activating this pathway on both ER stress and mitochondrial structure and function and its relationship to cellular function will be discussed in this presentation.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology