Role of adenosine monophosphate-activated protein kinase in the control of energy homeostasis.

摘要

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.