Role of adenosine monophosphate-activated protein kinase in the control of energy homeostasis.
OBJECTIVE
Adenosine monophosphate-activated protein kinase is involved in cellular energy homeostasis. This review will evaluate recent findings in terms of the importance of adenosine monophosphate-activated protein kinase as a potential target for the treatment of diseases such as obesity and type 2 diabetes.


RESULTS
Adenosine monophosphate-activated protein kinase is involved in the insulin-sensitizing action of adipocyte hormones, adiponectin and leptin and antidiabetic drugs. One important novelty is that adenosine monophosphate-activated protein kinase is part of the regulation cascade of food intake by hormones and substrates at the hypothalamic level. A global energy shortage stimulates adenosine monophosphate-activated protein kinase in hypothalamic nuclei, which then transmits a message of hunger to the organism. Finally, an adenosine monophosphate-activated protein kinase has been discovered. This kinase (LKB1) phosphorylates and activates adenosine monophosphate-activated protein kinase and 11 adenosine monophosphate-activated protein kinase-related kinases. LKB1 is continuously active and the activation of adenosine monophosphate-activated protein kinase by LKB1 is then secondary to an action of adenosine monophosphate on adenosine monophosphate-activated protein kinase rather than on LKB1.


CONCLUSIONS
The relationship between adenosine monophosphate-activated protein kinase activation and increased insulin sensitivity points to this enzyme as a potential target in type 2 diabetes. However, activation of adenosine monophosphate-activated protein kinase, although beneficial in terms of insulin sensitivity, might be detrimental because it can stimulate food intake. Conversely, adenosine monophosphate-activated protein kinase inhibition could decrease food intake and thus reduce obesity. Finally, adenosine monophosphate-activated protein kinase is a better target than LKB1 for the development of specific activating (or inhibiting) drugs.
Foufelle
Fabienne
F
INSERM Unit 671, University Pierre et Marie Curie, Centre de Recherches Biomedicales des Cordeliers, Paris, France.
Ferré
Pascal
P
D000249:Adenosine Monophosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*
D007328:Insulin; D000249:Adenosine Monophosphate; D011494:Protein Kinases