Signalling components involved in contraction-inducible substrate uptake into cardiac myocytes.
Glucose and long-chain fatty acids (LCFA) are two major substrates used by heart and skeletal muscle to support contractile activity. In quiescent cardiac myocytes a substantial portion of the glucose transporter GLUT4 and the putative LCFA transporter fatty acid translocase (FAT)/CD36 are stored in intracellular compartments. Induction of cellular contraction by electrical stimulation results in enhanced uptake of both glucose and LCFA through translocation of GLUT4 and FAT/CD36 respectively to the sarcolemma. The involvement of protein kinase A, AMP-activated protein kinase (AMPK), protein kinase C (PKC) isoforms and the extracellular signal-regulated kinases was evaluated in cardiac myocytes as candidate signalling enzymes involved in recruiting these transporters in response to contraction. The collected evidence excluded the involvement of PKA and implicated an important role for AMPK and for one (or more) PKC isoform(s) in contraction-induced translocation of both GLUT4 and FAT/CD36. The unravelling of further components along this contraction pathway can provide valuable information on the coordinated regulation of the uptake of glucose and of LCFA by an increase in mechanical activity of heart and skeletal muscle.
Luiken
Joost J F P
JJ
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, NL-6200 MD Maastricht, The Netherlands. j.luiken@gen.unimaas.nl
Coort
Susan L M
SL
Koonen
Debby P Y
DP
Bonen
Arend
A
Glatz
Jan F C
JF
D018955:CD36 Antigens / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000378:metabolism*; D020033:Protein Isoforms; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction
D018955:CD36 Antigens; D005227:Fatty Acids; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C495692:SLC2A4 protein, human; D011494:Protein Kinases; D005947:Glucose