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

Curr Opin Clin Nutr Metab Care. 2005 Jul;8(4):355-60. doi: 10.1097/01.mco.0000172572.18278.fc.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Adenosine Monophosphate / metabolism*
  • Adenosine Monophosphate / pharmacology
  • Animals
  • Energy Metabolism / physiology*
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Homeostasis / physiology
  • Humans
  • Insulin / metabolism*
  • Obesity / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism*

Substances

  • Insulin
  • Adenosine Monophosphate
  • Protein Kinases