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J Mol Endocrinol. 2016 Jul;57(1):R49-58. doi: 10.1530/JME-16-0073. Epub 2016 Apr 22.

Nuclear receptors and AMPK: can exercise mimetics cure diabetes?

Author information

1
Gene Expression LaboratorySalk Institute, La Jolla, California, USA Biomedical Sciences Graduate ProgramUC San Diego, La Jolla, California, USA.
2
Gene Expression LaboratorySalk Institute, La Jolla, California, USA.
3
Gene Expression LaboratorySalk Institute, La Jolla, California, USA Howard Hughes Medical InstituteSalk Institute, La Jolla, California, USA evans@salk.edu.

Abstract

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.

KEYWORDS:

AMPK; PGC1α; PPARs; diabetes; exercise mimetics; nuclear receptors; sirtuins

PMID:
27106806
PMCID:
PMC4929025
DOI:
10.1530/JME-16-0073
[Indexed for MEDLINE]
Free PMC Article

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