Function
AMPK acts as a metabolic master switch regulating several intracellular systems including the cellular uptake of glucose, the β-oxidation of fatty acids and the biogenesis of glucose transporter 4 (GLUT4) and mitochondria. The energy-sensing capability of AMPK can be attributed to its ability to detect and react to fluctuations in the AMP:ATP ratio that take place during rest and exercise (muscle stimulation). During muscle stimulation, AMP increases while ATP decreases, which changes AMPK into a good substrate for activation via an upstream kinase complex, AMPKK, or better, where binding of AMP renders activated AMPK that is phosphorylated at Thr-172 a worse substrate for protein phosphatase 2Calpha. AMPKK is a complex of three proteins, STE-related adaptor (STRAD), mouse protein 25 (MO25), and LKB1 (a serine/threonine kinase). During a bout of exercise, AMPK activity increases while the muscle cell experiences metabolic stress brought about by an extreme cellular demand for ATP. Upon activation, AMPK increases cellular energy levels by inhibiting anabolic energy consuming pathways (fatty acid synthesis, protein synthesis, etc.) and stimulating energy producing, catabolic pathways (fatty acid oxidation, glucose transport, etc.).
A recent JBC paper on mice at Johns Hopkins has shown that when the activity of brain AMPK was pharmacologically inhibited, the mice ate less and lost weight. When AMPK activity was pharmacologically raised (AICAR see below) the mice ate more and gained weight. Research in Britain has shown that the appetite-stimulating hormone ghrelin also affects AMPK levels. The antidiabetic drug metformin (Glucophage) acts by stimulating AMPK, leading to reduced glucose production in the liver and reduced insulin resistance in the muscle. (Metformin usually causes weight loss and reduced appetite, not weight gain and increased appetite, which is opposite of what might be expected given the Johns Hopkins mouse study results. )
A number of recent studies suggest that the botanical alkaloid berberine, also activates AMPK and glucose transport in muscles.
Read more about this topic: AMP-activated Protein Kinase
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