CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
artículos
Título:
Serum complexes of insulin-like growth factor-1 modulates skeletal integrity and carbohydrate metabolism
Autor/es:
YAKAR, S; ROSEN CJ; BOUXSEIN ML; HUI SUN; MEJIA W; KAWASHIMA Y; WU Y; EMERTON K; WILLIAMS V; JEPSEN K; SCHAFFLER MB; MAJESKA RJ; GAVRILOVA O; GUTIERREZ M; HWANG D; PENNISI P; FRYSTYK J; BOISCLAIR Y; PINTAR J; JASPER HG; DOMENÉ HM; COHEN P; CLEMMONS, D; LEROITH, D
Revista:
FASEB JOURNAL
Editorial:
The Federation of American Societies for Experimental Biology, Stanford University Libraries
Referencias:
Lugar: Bethesda MD; Año: 2008 vol. 23 p. 709 - 719
ISSN:
0892-6638
Resumen:
Serum insulin-like growth factor (IGF) -1 is secreted mainly by the liver and circulates bound to IGF-binding proteins (IGFBPs), either as binary complexes or ternary complexes with IGFBP-3 or IGFBP-5 and an acid-labile subunit (ALS). The purpose of this study was to genetically dissect the role of IGF-1 circulatory complexes in somatic growth, skeletal integrity, and metabolism. Phenotypic comparisons of controls and four mouse lines with genetic IGF-1 deficits-liver-specific IGF-1 deficiency (LID), ALS knockout (ALSKO), IGFBP-3 (BP3) knockout, and a triply deficient LID/ALSKO/BP3 line-produced several novel findings. 1) All deficient strains had decreased serum IGF-1 levels, but this neither predicted growth potential or skeletal integrity nor defined growth hormone secretion or metabolic abnormalities. 2) IGF-1 deficiency affected development of both cortical and trabecular bone differently, effects apparently dependent on the presence of different circulating IGF-1 complexes. 3) IGFBP-3 deficiency resulted in increased linear growth. In summary, each IGF-1 complex constituent appears to play a distinct role in determining skeletal phenotype, with different effects on cortical and trabecular bone compartments.-Yakar, S., Rosen, C. J., Bouxsein, M. L., Sun, H., Mejia, W., Kawashima, Y., Wu, Y., Emerton, K., Williams, V., Jepsen, K., Schaffler, M. B., Majeska, R. J., Gavrilova, O., Gutierrez, M., Hwang, D., Pennisi, P., Frystyk, J., Boisclair, Y., Pintar, J., Jasper, H., Domene, H., Cohen, P., Clemmons, D., LeRoith, D. Serum complexes of insulin-like growth factor-1 modulate skeletal integrity and carbohydrate metabolism.