Serum complexes of insulin‐like growth factor‐1 modulate skeletal integrity and carbohydrate metabolism

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...

Full description

Authors: 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 Alejandra; Frystyk, Jan; Boisclair, Yves; Pintar, John; Jasper, Hector Guillermo; Domene, Horacio Mario; Cohen, Pinchas; Clemmons, David; LeRoith, Derek
Format: Article
Status:Published version
Publication date:2008
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/103902
Online Access:http://hdl.handle.net/11336/103902
Access Level:Open access
Keyword:CORTICAL BONE
TRABECULAR BONE
OSTEOCLAST
OSTEOBLAST
TERNARY COMPLEX
BINARY COMPLEX
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
Summary: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.

Similar Items