Stimulation of myocyte insulin-responsive glucose transporters by the inhibition of fatty acid oxidation.
The effects of the fatty acid inhibitor 4-bromocrotonic acid (4-BCA) on glucose utilization was studied in isolated rat myocytes. In contrast to its potent inhibition of [1-14C]palmitate oxidation, 4-BCA strongly stimulated the oxidation of [1-14C]glucose and [2-14C]-pyruvate in a concentration-dependent manner. At a concentration of 300 microM, 4-BCA increased glucose oxidation threefold and that of pyruvate oxidation twofold. The rate of transport of [U-14C]-2-deoxyglucose was significantly stimulated by 4-BCA. The transport of 2-deoxyglucose was increased sevenfold with 200 microM 4-BCA, whereas insulin (10 microU)/ml enhanced 2-deoxyglucose transport twofold. The addition of insulin to myocytes preincubated with 4-BCA did not further increase glucose transport. Cytochalasin B and anti-GLUT 4 antibody decreased the 4-BCA-induced stimulation of glucose transport. These results suggest that the stimulation of 2-deoxy-glucose transport by 4-BCA occurs through an increase in the activity of insulin-responsive glucose transporters, GLUT 4, in the sarcolemmal membrane.
Abdel-aleem
S
S
Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Badr
M
M
Perez-Tamayo
R A
RA
Anstadt
M P
MP
Lowe
J E
JE
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003437:Crotonates / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D006321:Heart / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*
D003437:Crotonates; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010169:Palmitic Acids; D011773:Pyruvates; C495694:Slc2a4 protein, rat; C034444:4-bromocrotonic acid; D019308:Palmitic Acid; D003847:Deoxyglucose; D005947:Glucose