Activation of AMPK and its Impact on Exercise Capacity
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REVIEW ARTICLE
Activation of AMPK and its Impact on Exercise Capacity Ellen Niederberger1 • Tanya S. King1 • Otto Quintus Russe1 • Gerd Geisslinger1
Ó Springer International Publishing Switzerland 2015
Abstract Activation of the adenosine monophosphate (AMP)-activated kinase (AMPK) contributes to beneficial effects such as improvement of the hyperglycemic state in diabetes as well as reduction of obesity and inflammatory processes. Furthermore, stimulation of AMPK activity has been associated with increased exercise capacity. A study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR (5-amino1-b-D-ribofuranosyl-imidazole-4-carboxamide) increased the running capacity of mice without any training and thus, prompted the World Anti-Doping Agency (WADA) to include certain AMPK activators in the list of forbidden drugs. This raises the question as to whether all AMPK activators should be considered for registration or whether the increase in exercise performance is only associated with specific AMPK-activating substances. In this review, we intend to shed light on currently published AMPK-activating drugs, their working mechanisms, and their impact on body fitness. Key Points Adenosine monophosphate (AMP) activation is associated with beneficial effects such as lowering of blood glucose. Some, but not all, AMP kinase activators lead to improved exercise capacity.
& Ellen Niederberger [email protected] 1
Pharmazentrum Frankfurt/ZAFES, Institut fu¨r Klinische Pharmakologie, Klinikum der Goethe-Universita¨t Frankfurt, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
1 Introduction Exercise training, particularly endurance exercise, has been frequently associated with beneficial health effects. As endurance exercise improves metabolic as well as cardiovascular disturbances, patient-adapted endurance exercise is often recommended as a basic therapeutic action for these diseases. Physiological effects of endurance training comprise remodeling of muscles, which are composed of a number of different fibers, including red oxidative slowtwitch (type I), white oxidative/glycolytic fast-twitch (type IIa), oxidative fast-twitch (type IIx), and glycolytic fasttwitch (type IIb) myofibers. The slow-twitch fibers express high levels of fat-oxidizing enzymes, mitochondria, and slow contractile proteins. Fast-twitch myofibers are fastresistance or fast-fatigue fibers that express the fast contractile proteins but contain only a few mitochondria and metabolize glucose anaerobically. Endurance exercise leads to an increase in slow-twitch contractile proteins, mitochondrial biogenesis, and fatty acid oxidation, which change the skeletal muscles towards an oxidative slowtwitch phenotype with higher aerobic capacity [1, 2]. These changes are associated with increased insulin sensitivity and an overall improvement in glucose homeostasis and therefore, positively influence diabetes and obesity [3, 4]. However, quite a large number of people and/or patients with these d
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