The role of insulin receptor signaling in zebrafish embryogenesis
Open accessAbstract
Insulin receptor (IR) signaling is considered to be important in growth and development in addition to its major role in metabolic homeostasis. The metabolic role of insulin in carbohydrate and lipid metabolism is extensively studied. In contrast, the role of IR activation during embryogenesis is less understood. To address this, we examined the function of the IR during zebrafish development. Zebrafish express two isoforms of IR (insra and insrb). Both isoforms were cloned and show high homology to the human insulin receptor and can functionally substitute for the human IR in fibroblasts derived from insr gene-deleted mice. Gene expression studies reveal that these receptors are expressed at moderate levels in the central nervous system during development. Morpholino-mediated selective knockdown of each of the IR isoforms causes growth retardation and profound morphogenetic defects in the brain and eye. These results clearly demonstrate that IR signaling plays essential roles in vertebrate embryogenesis and growth.
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Human Insulin is active in zebrafish because its mature form shares extensive amino acid identity with zebrafish Insulin and was previously shown to activate zebrafish Insulin receptors.
“We suspected that human Insulin would be active in zebrafish because its mature form exhibits extensive amino acid identity (~77%) with that of zebrafish and it was previously shown to activate zebrafish Insulin receptors (Papasani et al., 2006; Toyoshima et al., 2008).”
From Retinal injury, growth factors, and cytokines converge on β-catenin and pStat3 signaling to stimulate retina regeneration (2014) · cites this paper as Toyoshima et al., 2008
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- Authors
- Toyoshima, Y., Monson, C., Duan, C., Wu, Y., Gao, C., Yakar, S., Sadler, K. C., & LeRoith, D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Mount Sinai Hospital (US)
- University of Michigan (US)
- Corresponding author
- LeRoith, Derek
- ORCID
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2008-08-07
- Volume
- 149
- Issue
- 12
- Pages
- 5996-6005
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2613066
- OpenAlex
- W2015316303
- Cited by
- 72
- References
- 32
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 2.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- insulin receptor signaling, zebrafish embryonic development, insulin receptor isoforms, brain development, eye development, growth retardation, central nervous system, morpholino knockdown
- MeSH terms
- Animals, Cell Line, Mutation, Receptor, Insulin, Zebrafish, Blotting, Western, Signal Transduction, In Situ Hybridization, Gene Expression Regulation, Developmental, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Mice
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