Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique

Abstract

IGF-I plays a direct role in whole body glucose homeostasis primarily by stimulating skeletal muscle glucose uptake. IGF-I is also involved in exercise induced muscle hypertrophy. Knowledge regarding local changes in muscle IGF-I bioavailability and its regulation by IGFBPs at rest and during exercise is limited. We have therefore explored changes in total IGF-I levels as well as circulating IGFBP levels and their post-translational modifications over an exercising leg. For the first time we have determined IGF-I levels in exercising skeletal muscle microdialysate in an attempt to assess local IGF-I bioavailability. Eighteen healthy young men performed one legged knee-extension exercise during 45 min. Blood samples were taken from the femoral artery and vein of the exercising leg. No significant differences between arterial and venous concentrations of total IGF-I or IGFBP-1 were detected over the leg at any time. IGF-I concentrations increased significantly during exercise in the artery but not in the vein. Total IGFBP-1 increased after exercise in both artery and vein. The increase in non-plus less phosphorylated forms of IGFBP-1 was less pronounced and did not reach statistical significance. The proportion of fragmented IGFBP-3 (IGFBP-3 proteolysis) assessed by Western immunoblotting did not change significantly during or after exercise. Although optimization and validation of IGF-I determinations in muscle microdialysate (md) will be required, our first results using this technique demonstrate a significant 2-fold increase in mdIGF-I collected during and after exercise. We conclude that determination of A-V-differences appears to be of limited value in the assessments of local muscle change in the IGF-system. A substantial release of IGF-I during short time is required to detect significant change in the large circulating store of IGF-I. We suggest that an optimized and validated microdialysis technique for determination of local IGF-I may be advantageous in future studies.