LKB1 and AMPK and the regulation of skeletal muscle metabolism

Curr Opin Clin Nutr Metab Care. 2008 May;11(3):227-32. doi: 10.1097/MCO.0b013e3282fb7b76.

Abstract

Purpose of review: To address the role of LKB1 and AMP-activated protein kinase (AMPK) in glucose transport, fatty acid oxidation, and metabolic adaptations in skeletal muscle.

Recent findings: Contraction-mediated skeletal muscle glucose transport is decreased in muscle-specific LKB1 knockout mice, but not in whole body AMPKalpha2 knockout mice or AMPKalpha2 inactive transgenic mice. Chronic activation of AMPK by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) and beta-guanadinopropionic acid enhances mitochondrial function in skeletal muscle, but AICAR or exercise-induced increases in mitochondrial markers are preserved in skeletal muscles from whole body AMPKalpha2 or muscle-specific LKB1 knockout mice. Pharmacological activation of AMPK increases glucose transport and fatty acid oxidation in skeletal muscle. Therefore, chronic activation of AMPK may be beneficial in the treatment of obesity and type 2 diabetes.

Summary: LKB1 and AMPK play important roles in regulating metabolism in resting and contracting skeletal muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • Animals
  • Enzyme Activation
  • Fatty Acids / metabolism*
  • Glucose / metabolism*
  • Humans
  • Mice
  • Mice, Knockout
  • Multienzyme Complexes / metabolism*
  • Muscle Contraction / physiology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Fatty Acids
  • Multienzyme Complexes
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • Glucose