Nuclear Receptors and AMPK: Can Exercise Mimetics Cure Diabetes?

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 article, we will 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 will also discuss evidence from clinical trials utilizing these compounds in human subjects to evaluate their efficacy in treating diabetes.