Calorie restriction increases cell surface GLUT-4 in insulin-stimulated skeletal muscle.
Reduced calorie intake [calorie restriction (CR); 60% of ad libitum (AL)] leads to enhanced glucose transport without altering total GLUT-4 glucose transporter abundance in skeletal muscle. Therefore, we tested the hypothesis that CR (20 days) alters the subcellular distribution of GLUT-4. Cell surface GLUT-4 content was higher in insulin-stimulated epitrochlearis muscles from CR vs. AL rats. The magnitude of this increase was similar to the CR-induced increase in glucose transport, and GLUT-4 activity (glucose transport rate divided by cell surface GLUT-4) was unaffected by diet. The CR effect was specific to the insulin-mediated pathway, as evidenced by the observations that basal glucose transport and cell surface GLUT-4 content, as well as hypoxia-stimulated glucose transport, were unchanged by diet. CR did not alter insulin's stimulation of insulin receptor substrate (IRS)-1-associated phosphatidylinositol 3-kinase (PI3K) activity. Muscle abundance of IRS-2 and p85 subunit of PI3K were unaltered by diet, but IRS-1 content was lower in CR vs. AL. These data demonstrate that, despite IRS-1-PI3K activity similar to AL, CR specifically increases insulin's activation of glucose transport by enhancing the steady-state proportion of GLUT-4 residing on the cell surface.
Dean
D J
DJ
Biodynamics Laboratory, Department of Kinesiology and Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Brozinick
J T
JT
Cushman
S W
SW
Cartee
G D
GD
D019325:3-O-Methylglucose / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001786:Blood Glucose / Q000032:analysis; D002462:Cell Membrane / Q000378:metabolism; D015331:Cohort Studies; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D019325:3-O-Methylglucose; D005947:Glucose