Alpha-lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle.
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.
Lee
Woo Je
WJ
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Song
Kee-Ho
KH
Koh
Eun Hee
EH
Won
Jong Chul
JC
Kim
Hyoun Sik
HS
Park
Hye-Sun
HS
Kim
Min-Seon
MS
Kim
Seung-Whan
SW
Lee
Ki-Up
KU
Park
Joong-Yeol
JY
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
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