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Normal growth and development in the absence of hepatic insulin-like growth factor I
Open accessAbstract
The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/ loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I.
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Citations
Cited by
Hayhurst, G. P., Lee, Y.-H., Lambert, G., Ward, J. M., & Gonzalez, F. J. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.4.1393-1403.2001 · Cited by 1,107
Trejo, J. L., Carro, E., & Torres-Alemán, I. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01628.2001 · Cited by 1,017
SOCS3 negatively regulates IL-6 signaling in vivo
Croker, B. A., Krebs, D. L., Zhang, J.-G., Wormald, S., Willson, T. A., Stanley, E. G., Robb, L., Greenhalgh, C. J., Förster, I., Clausen, B. E., et al. (2003) · Nature Immunology · doi:10.1038/ni931 · Cited by 840
Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models
Schiaffino, S., & Mammucari, C. (2011) · Skeletal Muscle · doi:10.1186/2044-5040-1-4 · Cited by 816
“This discrepancy was explained by the fact that a residual fraction of circulating IGF1 is detected in the liver-specific knockout [40,41] because of incomplete Igf1 gene excision [43].”
BackgroundCirculating Insulin-Like Growth Factor I Mediates Effects of Exercise on the Brain
Carro, E., Nuñez, A., Busiguina, S., & Torres-Aleman, I. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-08-02926.2000 · Cited by 762
Metadata
- Authors
- Yakar, S., Liu, J.-L., Stannard, B., Butler, A., Accili, D., Sauer, B., & LeRoith, D.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-06-22
- Volume
- 96
- Issue
- 13
- Pages
- 7324-7329
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2054121324
- Cited by
- 1,420
- References
- 0
- FWCI
- 46.81
- Type
- journal article
- Language
- en
- Open access
- green
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- Yakar, S., Liu, J.-L., Stannard, B., Butler, A., Accili, D., Sauer, B., & LeRoith, D. (1999). Normal growth and development in the absence of hepatic insulin-like growth factor I. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.13.7324
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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