FASEB J. Mp Biomedicals
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
fj.08-118976v1
23/3/709    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yakar, S.
Right arrow Articles by LeRoith, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yakar, S.
Right arrow Articles by LeRoith, D.
Published online before print October 24, 2008 as doi: 10.1096/fj.08-118976.

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

Shoshana Yakar, Clifford J. Rosen, Mary L. Bouxsein, Hui Sun, Wilson Mejia, Yuki Kawashima, Yingjie Wu, Kelly Emerton, Valerie Williams, Karl Jepsen, Mitchell B. Schaffler, Robert J. Majeska, Oksana Gavrilova, Mariana Gutierrez, David Hwang, Patricia Pennisi, Jan Frystyk, Yves Boisclair, John Pintar, Héctor Jasper, Horacio Domene, Pinchas Cohen, David Clemmons, and Derek LeRoith

E-mail contact: shoshana.yakar@mssm.edu

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.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
V. E DeMambro, M. Kawai, T. L Clemens, K. Fulzele, J. A Maynard, C. Marin de Evsikova, K. R Johnson, E. Canalis, W. G Beamer, C. J Rosen, et al.
A novel spontaneous mutation of Irs1 in mice results in hyperinsulinemia, reduced growth, low bone mass and impaired adipogenesis
J. Endocrinol., March 1, 2010; 204(3): 241 - 253.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. C. Fritton, Y. Kawashima, W. Mejia, H.-W. Courtland, S. Elis, H. Sun, Y. Wu, C. J. Rosen, D. Clemmons, and S. Yakar
The Insulin-like Growth Factor-1 Binding Protein Acid-labile Subunit Alters Mesenchymal Stromal Cell Fate
J. Biol. Chem., February 12, 2010; 285(7): 4709 - 4714.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Wu, H. Sun, S. Yakar, and D. LeRoith
Elevated Levels of Insulin-Like Growth Factor (IGF)-I in Serum Rescue the Severe Growth Retardation of IGF-I Null Mice
Endocrinology, September 1, 2009; 150(9): 4395 - 4403.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
C. Ohlsson, S. Mohan, K. Sjogren, A. Tivesten, J. Isgaard, O. Isaksson, J.-O. Jansson, and J. Svensson
The Role of Liver-Derived Insulin-Like Growth Factor-I
Endocr. Rev., August 1, 2009; 30(5): 494 - 535.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2008 by The Federation of American Societies for Experimental Biology.