Possible involvement of AMPK in acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in fast-twitch skeletal muscle

Metabolism. 2013 Nov;62(11):1633-40. doi: 10.1016/j.metabol.2013.06.010. Epub 2013 Jul 23.


Objective: The regulatory mechanisms responsible for acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in skeletal muscle remain unclear. 5'-adenosine-activated protein kinase (AMPK) is a key signaling molecule that regulates gene expression at the mRNA level. We examined whether AMPK activation is involved in acute exercise-induced expression of MCT1 and MCT4 mRNA in fast-twitch muscle.

Materials/methods: Male Sprague-Dawley rats were subjected to an acute bout of either 5min high-intensity intermittent swimming (HIS) or 6-h low-intensity prolonged swimming (LIS). The effects of acute exercise on the phosphorylation of AMPK (p-AMPK), calcium/calmodulin pendent kinase II (p-CaMKII), p38 mitogen-activated protein kinase (p-p38MAPK), and MCTs mRNA were analyzed in vivo. To observe the direct effects of AMPK activation on MCTs mRNA, the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), caffeine, and dantrolene were analyzed in vitro using an isolated muscle incubation model.

Results: The p-AMPK increased in response to both HIS and LIS, although the p-CaMKII and p-p38MAPK were increased only following HIS. Irrespective of exercise intensity, MCT1 and MCT4 mRNA was also transiently upregulated by both HIS and LIS. Direct exposure of the epitrochlearis muscle to 0.5mmol/L AICAR or 1mmol/L caffeine, which activated p-AMPK increased both MCT1 and MCT4 mRNA levels. When pAMPK was inhibited by dantrolene, neither MCT1 nor MCT4 mRNA was increased.

Conclusion: These results suggest that acute exercise-induced increases in MCT1 and MCT4 mRNA expression may be possibly mediated by AMPK activation, at least in part in fast-twitch muscle.

Keywords: 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside; 5′-adenosine-activated protein kinase; ACC; AICAR; AMPK; Acetyl-CoA carboxylase; Acute exercise; CaMKII; MCT; MCTs; PGC1α; Signaling; Skeletal muscle; calcium/calmodulin-dependent kinase II; monocarboxylate transporters; p38 mitogen-activated protein kinase; p38MAPK; peroxisome proliferator activated receptor gamma coactivator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Dantrolene / pharmacology
  • Gene Expression Regulation / drug effects
  • Male
  • Monocarboxylic Acid Transporters / metabolism*
  • Muscle Proteins / metabolism*
  • Muscle Relaxants, Central / pharmacology
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / physiology
  • Phosphorylation / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Ribonucleotides / pharmacology
  • Signal Transduction / drug effects
  • Swimming / physiology*
  • Symporters / metabolism*
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • Muscle Relaxants, Central
  • RNA, Messenger
  • Ribonucleotides
  • Slc16a3 protein, rat
  • Symporters
  • monocarboxylate transport protein 1
  • Aminoimidazole Carboxamide
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Dantrolene