title: Insulin stimulates L-carnitine accumulation in human skeletal muscle.
abstract: Increasing skeletal muscle carnitine content may alleviate the decline in muscle fat oxidation seen during intense exercise. Studies to date, however, have failed to increase muscle carnitine content, in healthy humans, by dietary or intravenous L-carnitine administration. We hypothesized that insulin could augment Na+-dependent skeletal muscle carnitine transport. On two randomized visits, eight healthy men underwent 5 h of intravenous L-carnitine infusion with serum insulin maintained at fasting (7.4+/-0.4 mIU*l(-1)) or physiologically high (149.2+/-6.9 mIU*l(-1)) concentrations. The combination of hypercarnitinemia (approximately 500 micromol*l(-1)) and hyperinsulinemia increased muscle total carnitine (TC) content from 22.0 +/- 0.9 to 24.7 +/- 1.4 mmol*(kg dm)(-1) (P<0.05) and was associated with a 2.3 +/- 0.3-fold increase in carnitine transporter protein (OCTN2) mRNA expression (P<0.05). Hypercarnitinemia in the presence of a fasting insulin concentration had no effect on either of these parameters. This study demonstrates that insulin can acutely increase muscle TC content in humans during hypercarnitinemia, which is associated with an increase in OCTN2 transcription. These novel findings may be of importance to the regulation of muscle fat oxidation during exercise, particularly in obesity and type 2 diabetes where it is known to be impaired.
authors.affiliation: Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, NG7 2UH, UK.
authors.forename: Francis B
authors.initials: FB
authors.lastname: Stephens
authors.forename: Dumitru
authors.initials: D
authors.lastname: Constantin-Teodosiu
authors.forename: David
authors.initials: D
authors.lastname: Laithwaite
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Simpson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Greenhaff
mesh_terms: D000328:Adult; D002331:Carnitine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000074058:Solute Carrier Family 22 Member 5; D014158:Transcription, Genetic
chemical_list: D007328:Insulin; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D012964:Sodium; D002331:Carnitine