Context. Insulin stimulated glucose uptake in skeletal muscle is mediated through the translocation of the insulin sensitive glucose transporter (GLUT4)-containing vesicles to the plasma membrane. Thus, skeletal muscle GLUT4 content plays an important role for whole body insulin sensitivity.

Objectives. 1. To examine the relative impact of genetic vs. environmental factors on skeletal muscle GLUT4 mRNA expression using biometric modeling. 2. To identify factors influencing a) the expression of GLUT4 and b) insulin stimulated whole body metabolism.

Design. We measured GLUT4 mRNA expression in biopsies from young and elderly monozygotic (MZ) and dizygotic (DZ) twins before and during a 2-h hyperinsulinaemic euglycaemic clamp including [3-³H]-tritiated glucose and indirect calorimetry.

Participants. A random sample of young (22-31 yr, n = 89) and elderly (57-66 yr, n = 69) same sex MZ and DZ twin pairs identified through The Danish Twin Register.

Results. We found a major genetic component in the control of basal and insulin stimulated GLUT4 mRNA expression in young and elderly twins. The GLUT4 gene expression increased upon insulin stimulation in both young and elderly twins. Multiple regression analysis revealed that both basal and insulin stimulated GLUT4 mRNA expression was positively related to birth weight and VO₂max, and higher in MZ vs. DZ twins as well as in males vs. females. Both basal and insulin stimulated expression of GLUT4 was independently and significantly related to whole body in vivo insulin action, non-oxidative glucose metabolism and glucose oxidation.

Conclusion. We show that skeletal muscle GLUT4 gene expression in twins is significantly and independently related to glucose metabolism and is determined by both genetic and non-genetic factors including zygosity and birth weight.