Local changes in the insulin-like growth factor system in human skeletal muscle assessed by microdialysis and arterio-venous differences technique.
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 45min. 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.
Berg
U
U
Department of Woman and Child Health, Pediatric Endocrinology Unit, Karolinska Institute, Astrid Lindgren Children's Hospital, Stockholm, Sweden. ulrika.berg@ki.se
Gustafsson
T
T
Sundberg
C J
CJ
Carlsson-Skwirut
C
C
Hall
K
K
Jakeman
P
P
Bang
P
P
D000328:Adult; D001808:Blood Vessels / Q000737:chemistry; D015444:Exercise; D005263:Femoral Artery / Q000502:physiology; D005268:Femoral Vein / Q000502:physiology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000032:analysis; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007866:Leg / Q000098:blood supply; D008297:Male; D017551:Microdialysis / Q000379:methods*; D018482:Muscle, Skeletal / Q000098:blood supply*; D012420:Running / Q000502:physiology; D013002:Somatomedins / Q000032:analysis*
D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I