title: Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle.
abstract: 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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Song
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Koh
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Won
authors.forename: Hyoun Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Min-Seon
authors.initials: MS
authors.lastname: Kim
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D009097:Multienzyme Complexes; D014280:Triglycerides; D019344:Lactic Acid; D008063:Thioctic Acid; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose