To elucidate the functional role of IGFBP-2 for in vivo skeletal muscle growth and function, skeletal muscle cellularity and metabolism as well as body growth and composition have been studied in a transgenic mouse model overexpressing IGFBP-2. Postnatal growth rate of transgenic mice (n=20) was clearly reduced from day 21 of age by 68% (P<0.05) compared with non-transgenic controls (n=37). At the final day of live (day 72 of age) body protein and moisture were lower, whereas fat percentage was higher in the IGFBP-2 transgenes (P<0.05). The weights of the lower leg and of the M. rectus femoris (RF) were reduced by 14% (P<0.0001), which was associated with higher DNA (P<0.05) at unchanged RNA and protein concentrations in RF. The reduction in muscle mass resulted mainly from slower growth of myofibres in size as seen from smaller cross sectional areas (by 12%; P<0.01), but not from decreases in the number of fibres. Analyses of metabolic fibre type composition and enzyme activities revealed that muscle metabolism was shifted to the glycolytic pathway of energy generation. The proportion of white (glycolytic) fibres was increased at the expense of intermediate (oxidative/glycolytic) fibres and, likewise, the activity of lactate dehydrogenase (LDH) was elevated (P<0.01). All differences observed between transgenic and non-transgenic mice were more pronounced in males as derived from significant genotype by sex interactions. The results suggest that IGBP-2 inhibits postnatal skeletal muscle growth and modifies muscle metabolism.
03 - 07 May 2008
European Society of Endocrinology