The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease
Abstract
In mammals, the insulin receptor (IR) gene has acquired an additional exon, exon 11. This exon may be skipped in a developmental and tissue-specific manner. The IR, therefore, occurs in two isoforms (exon 11 minus IR-A and exon 11 plus IR-B). The most relevant functional difference between these two isoforms is the high affinity of IR-A for IGF-II. IR-A is predominantly expressed during prenatal life. It enhances the effects of IGF-II during embryogenesis and fetal development. It is also significantly expressed in adult tissues, especially in the brain. Conversely, IR-B is predominantly expressed in adult, well-differentiated tissues, including the liver, where it enhances the metabolic effects of insulin. Dysregulation of IR splicing in insulin target tissues may occur in patients with insulin resistance; however, its role in type 2 diabetes is unclear. IR-A is often aberrantly expressed in cancer cells, thus increasing their responsiveness to IGF-II and to insulin and explaining the cancer-promoting effect of hyperinsulinemia observed in obese and type 2 diabetic patients. Aberrant IR-A expression may favor cancer resistance to both conventional and targeted therapies by a variety of mechanisms. Finally, IR isoforms form heterodimers, IR-A/IR-B, and hybrid IR/IGF-IR receptors (HR-A and HR-B). The functional characteristics of such hybrid receptors and their role in physiology, in diabetes, and in malignant cells are not yet fully understood. These receptors seem to enhance cell responsiveness to IGFs.
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Cites
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Cited by
Diamanti-Kandarakis, E., & Dunaif, A. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1034 · Cited by 1,947
Obesity and cancer risk: Emerging biological mechanisms and perspectives
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S., & Dalamaga, M. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.001 · Cited by 1,567
Function of alternative splicing
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The insulin and insulin-like growth factor receptor family in neoplasia: an update
Pollak, M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3215 · Cited by 1,116
Vigneri, P., Frasca, F., Sciacca, L., Pandini, G., & Vigneri, R. (2009) · Endocrine Related Cancer · doi:10.1677/erc-09-0087 · Cited by 1,009
Metadata
- Authors
- Belfiore, A., Frasca, F., Pandini, G., Sciacca, L., & Vigneri, R.
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2009-10-01
- Volume
- 30
- Issue
- 6
- Pages
- 586-623
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- OpenAlex
- W1997146974
- Cited by
- 1,033
- References
- 22
- FWCI
- 42.19
- Type
- journal article
- Language
- en
- Open access
- closed
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- Belfiore, A., Frasca, F., Pandini, G., Sciacca, L., & Vigneri, R. (2009). Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease. Endocrine Reviews. https://doi.org/10.1210/er.2008-0047
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