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Serum complexes of insulin‐like growth factor‐1 modulate skeletal integrity and carbohydrate metabolism
Author(s) -
Yakar Shoshana,
Rosen Clifford J.,
Bouxsein Mary L.,
Sun Hui,
Mejia Wilson,
Kawashima Yuki,
Wu Yingjie,
Emerton Kelly,
Williams Valerie,
Jepsen Karl,
Schaffler Mitchell B.,
Majeska Robert J.,
Gavrilova Oksana,
Gutierrez Mariana,
Hwang David,
Pennisi Patricia,
Frystyk Jan,
Boisclair Yves,
Pintar John,
Jasper Hector,
Domene Horacio,
Cohen Pinchas,
Clemmons David,
LeRoith Derek
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-118976
Subject(s) - endocrinology , medicine , growth factor , insulin like growth factor , phenotype , insulin like growth factor binding protein , biology , somatomedin , metabolism , insulin like growth factor 2 , somatic cell , chemistry , hormone , receptor , growth hormone , biochemistry , gene
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. FASEB J. 23, 709–719 (2009)