AMPK, insulin resistance, and the metabolic syndrome
Neil B. Ruderman, … , Marc Prentki, José M. Cacicedo
Neil B. Ruderman, … , Marc Prentki, José M. Cacicedo
Published July 1, 2013
Citation Information: J Clin Invest. 2013;123(7):2764-2772. https://doi.org/10.1172/JCI67227.
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Science in Medicine

AMPK, insulin resistance, and the metabolic syndrome

Abstract

Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as are central adiposity, dyslipidemia, and a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, and certain cancers. Regular exercise and calorie restriction have long been known to increase insulin sensitivity and decrease the prevalence of these disorders. The subsequent identification of AMP-activated protein kinase (AMPK) and its activation by exercise and fuel deprivation have led to studies of the effects of AMPK on both IR and metabolic syndrome–related diseases. In this review, we evaluate this body of literature, with special emphasis on the hypothesis that dysregulation of AMPK is both a pathogenic factor for these disorders in humans and a target for their prevention and therapy.

Authors

Neil B. Ruderman, David Carling, Marc Prentki, José M. Cacicedo

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Figure 3

Proposed interrelations of AMPK and sirtuins 1 and 3 (SIRTs) with oxidative and ER stress and inflammation.

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Proposed interrelations of AMPK and sirtuins 1 and 3 (SIRTs) with oxidat...
AMPK and SIRT1 both activate each other and diminish oxidative and ER stress and low-grade inflammation in various settings. Conversely, oxidative and ER stress and inflammation, which activate each other, appear to diminish AMPK and SIRT1. In principle, any of these factors could be targeted to combat IR and the development of metabolic syndrome–associated disorders; however, to date, the most success has been observed with therapies that target AMPK.