The AMP-activated protein kinase: more than an energy sensor

The AMPK (AMP-activated protein kinase) is a highly conserved eukaryotic protein serine/threonine kinase. It mediates a nutrient signalling pathway that senses cellular energy status and was appropriately called the fuel gauge of the cell. At the cellular level, AMPK controls energy homoeostasis by switching on catabolic ATP-generating pathways, while switching off anabolic ATP-consuming processes. Its effect on energy balance extends to whole-body energy homoeostasis, because, in the hypothalamus, it integrates nutritional and hormonal signals that control food intake and body weight. The interest in AMPK also stems from the demonstration of its insulin-independent stimulation of glucose transport in skeletal muscle during exercise. Moreover, the potential importance of AMPK in metabolic diseases is supported by the notion that AMPK mediates the anti-diabetic action of biguanides and thiazolidinediones and that it might be involved in the metabolic syndrome. Finally, the more recent demonstration that AMPK activation could occur independently of changes in cellular energy status, suggests that AMPK action extends to the control of non-metabolic functions.