Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 57, Issue 1, Pages R49-R58Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-16-0073
Keywords
nuclear receptors; PPARs; AMPK; PGC1 alpha; sirtuins; exercise mimetics; diabetes
Categories
Funding
- U.S. National Institutes of Health [DK057978, DK090962, HL088093, HL105278, CA014195, ES010337]
- Glenn Foundation for Medical Research
- Leona M. and Harry B. Helmsley Charitable Trust [2012-PG-MED002]
- Ipsen/Biomeasure
- Ellison Medical Foundation
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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.
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