Acylation-stimulating protein (ASP) regulates glucose transport in the rat L6 muscle cell line.
Acylation-stimulating protein (ASP), a human plasma protein, is a potent stimulator of triglyceride synthesis and glucose transport in both human adipocytes and fibroblasts. The purpose of the present in vitro study was to examine the effect of ASP on glucose transport in muscle cells. ASP stimulated 2-deoxy-glucose transport (2-DG) in differentiated rat L6 myotubes in a time (30 min to 24 h) and concentration dependent manner (97% increase). The magnitude of the ASP effect on glucose transport was comparable to the time- and concentration-dependent effects seen with insulin (125% increase), but was additive to insulin, pointing to involvement of differential signalling pathways. ASP stimulation was dependent on cell differentiation in that glucose transport increased by only 12% in myoblasts, comparable to the effect of insulin in myoblasts (15% increase) demonstrating selective responsiveness of the differentiated myotubes to ASP and insulin. The mechanism for the ASP induced increase in glucose transport was also examined. ASP increased the Vmax for 2-DG transport by 183% (4.02 vs. 1.42 nmol/mg cell protein/30 s; ASP vs. Control, respectively). This could be explained by an increased translocation of glucose transporters (GLUT 1, GLUT 4 and GLUT 3) to the plasma membrane surface as demonstrated by Western analysis (+43% P < 0.05, +30% P < 0.05, and +49% P < 0.05, respectively). The effects of ASP were equal to those of insulin (+47%, +26% and +53% for GLUT 1, GLUT 4 and GLUT 3, respectively) and in all cases were paralleled by comparable glucose transport increases under the same incubation conditions. After long-term stimulation (24 h), Western analysis indicated that ASP had a permissive effect on insulin stimulated increases in total GLUT3 and GLUT4 cellular transporter content. These results suggest that muscle is also responsive to ASP and that ASP may play a role in glucose metabolism in both muscle and adipose tissue.
Tao
Y
Y
McGill Unit for the Prevention of Cardiovascular Disease, Royal Victoria Hospital, Montreal, Que., Canada.
Cianflone
K
K
Sniderman
A D
AD
Colby-Germinario
S P
SP
Germinario
R J
RJ
D000818:Animals; D001692:Biological Transport; D001798:Blood Proteins / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015926:Complement C3a / Q000031:analogs & derivatives*; D003847:Deoxyglucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D051381:Rats
D001798:Blood Proteins; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C495694:Slc2a4 protein, rat; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D003847:Deoxyglucose; D005947:Glucose