Nuclear receptors and AMPK: can exercise mimetics cure diabetes?

    1. Ronald M Evans1,3
    1. 1Gene Expression Laboratory, Salk Institute, La Jolla, California, USA
    2. 2Biomedical Sciences Graduate Program, UC San Diego, La Jolla, California, USA
    3. 3Howard Hughes Medical Institute, Salk Institute, La Jolla, California, USA
    1. Correspondence should be addressed to R M Evans; Email: evans{at}


    Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as ‘exercise mimetics’, have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this review, we highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We also discuss evidence from clinical trials using these compounds in human subjects to evaluate their efficacy in treating diabetes.

    • Received 12 April 2016
    • Accepted 19 April 2016
    • Made available online as an Accepted Preprint 1 July 2016
    | Table of Contents