Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle

Biochem Biophys Res Commun. 2005 Jul 8;332(3):885-91. doi: 10.1016/j.bbrc.2005.05.035.


Triglyceride accumulation in skeletal muscle contributes to insulin resistance in obesity. We recently showed that alpha-lipoic acid (ALA) reduces body weight and prevents the development of diabetes in diabetes-prone obese rats by reducing triglyceride accumulation in non-adipose tissues. AMP-activated protein kinase (AMPK) is a major regulator of cellular energy metabolism. We examined whether ALA lowers triglyceride accumulation in skeletal muscle by activating AMPK. Alpha2-AMPK activity was decreased in obese rats compared to control rats. Administration of ALA to obese rats increased insulin-stimulated glucose disposal in whole body and in skeletal muscle. ALA also increased fatty acid oxidation and activated AMPK in skeletal muscle. Adenovirus-mediated administration of dominant negative AMPK into skeletal muscle prevented the ALA-induced increases in fatty acid oxidation and insulin-stimulated glucose uptake. These results suggest that ALA-induced improvement of insulin sensitivity is mediated by activation of AMPK and reduced triglyceride accumulation in skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Diabetes Mellitus, Type 2 / etiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Enzyme Activation / drug effects
  • Fatty Acids / metabolism
  • Glucose / metabolism
  • Insulin Resistance / physiology*
  • Lactic Acid / blood
  • Male
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism*
  • Oxidation-Reduction
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Rats
  • Rats, Inbred OLETF
  • Thioctic Acid / pharmacology*
  • Triglycerides / metabolism


  • Fatty Acids
  • Multienzyme Complexes
  • Triglycerides
  • Lactic Acid
  • Thioctic Acid
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Glucose