Unraveling the actions of AMP-activated protein kinase in metabolic diseases: Systemic to molecular insights

Metabolism. 2016 May;65(5):634-645. doi: 10.1016/j.metabol.2016.01.005. Epub 2016 Jan 14.

Abstract

AMP-activated protein kinase (AMPK) plays a critical role both in sensing and regulating cellular energy state. In experimental animals, its activation has been shown to reduce the risk of obesity and diabetes-related co-morbidities such as insulin resistance, the metabolic syndrome and atherosclerotic cardiovascular disease. However, in humans, AMPK activation alone often does not completely resolve these conditions. Thus, an improved understanding of AMPK action and regulation in metabolic and other diseases is needed. Herein, we provide a brief description of the enzymatic regulation of AMPK and review its role in maintaining energy homeostasis. We then discuss tissue-specific actions of AMPK that become distorted during such conditions as obesity, type 2 diabetes and certain cancers. Finally, we explore recent findings regarding the interactions of AMPK with mammalian target of rapamycin complex 1 and the lysosome and discuss how changes in these relationships during overnutrition may lead to AMPK dysfunction. A more thorough understanding of AMPK's molecular interactions during diseases of overnutrition may provide key insights for the development of AMPK-based combinatorial treatments for metabolic disease.

Keywords: AMPK; Insulin resistance; Lysosome; Type 2 diabetes; mTORC1.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Energy Intake
  • Energy Metabolism*
  • Glucose Metabolism Disorders / enzymology*
  • Glucose Metabolism Disorders / metabolism
  • Humans
  • Insulin Resistance*
  • Lysosomes / enzymology
  • Lysosomes / metabolism
  • Mechanistic Target of Rapamycin Complex 1
  • Models, Biological*
  • Multiprotein Complexes / metabolism
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / metabolism
  • Neoplasms / enzymology*
  • Neoplasms / metabolism
  • Obesity / enzymology*
  • Obesity / metabolism
  • Organ Specificity
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Multiprotein Complexes
  • Neoplasm Proteins
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases