Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle.
GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8 younger (29 yr) and 8 older (64 yr) healthy subjects, and estimates of GLUT-4 expression in individual fibers were obtained by combining immunohistochemistry and stereology. GLUT-4 was more abundantly expressed in slow compared with fast muscle fibers in both younger (P < 0.007) and older (P < 0. 001) subjects. A 25% reduction of GLUT-4 density in fast fibers (P < 0.001) and an unchanged GLUT-4 density in slow fibers were demonstrated in older compared with younger subjects. Insulin-stimulated glucose uptake rates measured by hyperinsulinemic, euglycemic clamp were not correlated with the fraction of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers.
Gaster
M
M
Departments of Pathology and of Endocrinology, Odense University Hospital, DK-5000 Odense, Denmark. janne.dhyr@ouh.dk
Poulsen
P
P
Handberg
A
A
Schroder
H D
HD
Beck-Nielsen
H
H
D000328:Adult; D000375:Aging; D001706:Biopsy; D015153:Blotting, Western; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000032:analysis*; D018656:Muscle Fibers, Fast-Twitch / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D005947:Glucose