APMIS 110: 611–9, 2002 Copyright C APMIS 2002 Printed in Denmark . All rights reserved ISSN 0903-4641 GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres M. GASTER, 1,2 W. VACH, 3 H. BECK-NIELSEN 2 and H. D. SCHRØDER 1 1 Dept. of Pathology, 2 Dept. of Endocrinology, Odense University Hospital. 3 Department of Statistics and Demography, University of Southern Denmark, Denmark Gaster M, Vach W Beck-Nielsen H and Schrøder HD. GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres. APMIS 2002;110:611–9. In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane, GLUT4 was more abundantly expressed in slow as compared to fast fibres at the same fibre diameter (p0.01) and the GLUT4 expression increased with increasing fibre radius indepen- dently of fibre type (p0.01). The GLUT4 density at the surface of slow fibres of both diabetic and obese was reduced compared to control subjects at the same diameter (p∞0.001). Fast fibres in obese and type 2 diabetic subjects expressed a fibre-volume-dependent GLUT4 expression (p0.001), while this did not reach significance in slow fibres (obese pΩ0.18 and diabetic pΩ0.06). Our results show that increasing fibre volume is associated with increasing GLUT4 expression in both slow and fast fibres. Based on the possible dependency of GLUT4 expression on volume, we hypothesize that the reduced GLUT4 expression in obesity and type 2 diabetes may partly be compensated for by physical activity. Key words: Glucose transporters; muscle fibres; immunohistochemistry; stereology; human. Michael Gaster, Dept. of Pathology, Odense University Hospital, DK-5000 Odense, Denmark. e-mail: marianne.abrahamsen/ouh.fyns-amt.dk It is mainly the glucose transporter protein GLUT4 that mediates glucose transport across the cell membrane of skeletal muscle (1, 2). In- sulin and muscle fibre contractions induce translocation of GLUT4 from intracellular storage vesicles to the plasma membrane and to the transverse tubules (3–5). We have recently developed a sensitive method which allows esti- mation of GLUT4 density in individually typed skeletal muscle fibres by a combination of im- munohistochemistry and stereology (6). We found a higher GLUT4 expression per fibre vol- ume in slow, compared to fast, twitch muscle fibres in young and older healthy subjects (6) Received March 4, 2002. Accepted June 1, 2002. 611 and in obese subjects (7). Type II diabetic pa- tients expressed a lower GLUT4 density in slow compared to fast fibres (7). In our first study (6) the diameters of slow and fast fibres were simi- lar and, because of this, the observed fibre-re- lated differences in GLUT4 immunoreactivity per fibre volume could be extended to include a fibre-type-related difference per surface unit at the sarcolemma of muscle fibres. However, the GLUT4 density per volume in slow fibres was unchanged in trained subjects compared to con- trol subjects (8), and further the slow fibre di- ameters were increased in trained athletes com- pared to controls, indicating that GLUT4 ex- pression along the plasma membrane of slow twitch fibres in trained muscles must be in- creased (8). We speculated that there was an as-