Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease
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...
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description | 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.
Recent insights indicate that insulin receptor isoform A or B expression influences metabolic and non-metabolic effects of insulin and insulin-like growth factors in target tissues. |
doi_str_mv | 10.1210/er.2008-0047 |
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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.
Recent insights indicate that insulin receptor isoform A or B expression influences metabolic and non-metabolic effects of insulin and insulin-like growth factors in target tissues.</description><identifier>ISSN: 0163-769X</identifier><identifier>EISSN: 1945-7189</identifier><identifier>DOI: 10.1210/er.2008-0047</identifier><identifier>PMID: 19752219</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Alternative Splicing ; Animals ; Beta cells ; Cancer ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - metabolism ; Embryogenesis ; Embryonic growth stage ; Fetuses ; Growth and Development ; Growth factors ; Humans ; Hybrids ; Hyperinsulinemia ; Insulin ; Insulin receptors ; Insulin resistance ; Insulin-like growth factor I receptors ; Insulin-like growth factor II ; Insulin-Like Growth Factor II - metabolism ; Insulin-like growth factors ; Isoforms ; Molecular Structure ; Myotonic Dystrophy - metabolism ; Neoplasms - metabolism ; Neoplasms - therapy ; Physiology ; Protein Isoforms - metabolism ; Receptor, Insulin - chemistry ; Receptor, Insulin - genetics ; Receptor, Insulin - metabolism ; Receptor, Insulin - physiology ; Receptors ; Receptors, Somatomedin - metabolism ; Signal Transduction</subject><ispartof>Endocrine reviews, 2009-10, Vol.30 (6), p.586-623</ispartof><rights>Copyright © 2009 by The Endocrine Society 2009</rights><rights>Copyright © 2009 by The Endocrine Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5432-5a9ed0d0fcd35a21d246f703dec8fc515a37ddda3e22720054e1ffdd3e0bff7b3</citedby><cites>FETCH-LOGICAL-c5432-5a9ed0d0fcd35a21d246f703dec8fc515a37ddda3e22720054e1ffdd3e0bff7b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19752219$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Belfiore, Antonino</creatorcontrib><creatorcontrib>Frasca, Francesco</creatorcontrib><creatorcontrib>Pandini, Giuseppe</creatorcontrib><creatorcontrib>Sciacca, Laura</creatorcontrib><creatorcontrib>Vigneri, Riccardo</creatorcontrib><title>Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease</title><title>Endocrine reviews</title><addtitle>Endocr Rev</addtitle><description>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.
Recent insights indicate that insulin receptor isoform A or B expression influences metabolic and non-metabolic effects of insulin and insulin-like growth factors in target tissues.</description><subject>Alternative Splicing</subject><subject>Animals</subject><subject>Beta cells</subject><subject>Cancer</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Embryogenesis</subject><subject>Embryonic growth stage</subject><subject>Fetuses</subject><subject>Growth and Development</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Hybrids</subject><subject>Hyperinsulinemia</subject><subject>Insulin</subject><subject>Insulin receptors</subject><subject>Insulin resistance</subject><subject>Insulin-like growth factor I receptors</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - metabolism</subject><subject>Insulin-like growth factors</subject><subject>Isoforms</subject><subject>Molecular Structure</subject><subject>Myotonic Dystrophy - metabolism</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - therapy</subject><subject>Physiology</subject><subject>Protein Isoforms - metabolism</subject><subject>Receptor, Insulin - chemistry</subject><subject>Receptor, Insulin - genetics</subject><subject>Receptor, Insulin - metabolism</subject><subject>Receptor, Insulin - physiology</subject><subject>Receptors</subject><subject>Receptors, Somatomedin - metabolism</subject><subject>Signal Transduction</subject><issn>0163-769X</issn><issn>1945-7189</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc1v1DAQxS0EotvCjTOKxIFL3fojWcdHVGi70kogBBI3y2uP2bTZOHgSrfa_x2EjVqrgYsvj3zy9eUPIG86uuODsGtKVYKymjJXqGVlwXVZU8Vo_JwvGl5Kqpf5xRs4RH1hGWK1fkjOuVSUE1wsyrDoc26YrvoKDfoipWGEMMe2wsJ0vnv5ezwW6bh6huEtxP2yLW-umxr8K94dNajwWue_L9oBNbOPPwx-5jw2CRXhFXgTbIrye7wvy_fbTt5t7uv58t7r5sKauKqWgldXgmWfBeVlZwb0ol0Ex6cHVwVW8slJ5760EIVTOoCqBh-C9BLYJQW3kBXl_1O1T_DUCDmbXoIO2tR3EEY2SOY9SapXJd0_IhzimLpszkgtdL3PCLFOXR8qliJggmD41O5sOhjMzLcNAMtMyzLSMjL-dRcfNDvwJntPPQHkE9rEdIOFjO-6zwhZsO2yzBmOy0ppmRc2nF50OcRorjv3_HNDZgTyS0PnoUtNBnwDxNNw_ff8GppOy6A</recordid><startdate>200910</startdate><enddate>200910</enddate><creator>Belfiore, Antonino</creator><creator>Frasca, Francesco</creator><creator>Pandini, Giuseppe</creator><creator>Sciacca, Laura</creator><creator>Vigneri, Riccardo</creator><general>Endocrine Society</general><general>Oxford University Press</general><general>Copyright by The Endocrine Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>200910</creationdate><title>Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease</title><author>Belfiore, Antonino ; Frasca, Francesco ; Pandini, Giuseppe ; Sciacca, Laura ; Vigneri, Riccardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5432-5a9ed0d0fcd35a21d246f703dec8fc515a37ddda3e22720054e1ffdd3e0bff7b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Alternative Splicing</topic><topic>Animals</topic><topic>Beta cells</topic><topic>Cancer</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Embryogenesis</topic><topic>Embryonic growth stage</topic><topic>Fetuses</topic><topic>Growth and Development</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Hybrids</topic><topic>Hyperinsulinemia</topic><topic>Insulin</topic><topic>Insulin receptors</topic><topic>Insulin resistance</topic><topic>Insulin-like growth factor I receptors</topic><topic>Insulin-like growth factor II</topic><topic>Insulin-Like Growth Factor II - metabolism</topic><topic>Insulin-like growth factors</topic><topic>Isoforms</topic><topic>Molecular Structure</topic><topic>Myotonic Dystrophy - metabolism</topic><topic>Neoplasms - metabolism</topic><topic>Neoplasms - therapy</topic><topic>Physiology</topic><topic>Protein Isoforms - metabolism</topic><topic>Receptor, Insulin - chemistry</topic><topic>Receptor, Insulin - genetics</topic><topic>Receptor, Insulin - metabolism</topic><topic>Receptor, Insulin - physiology</topic><topic>Receptors</topic><topic>Receptors, Somatomedin - metabolism</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Belfiore, Antonino</creatorcontrib><creatorcontrib>Frasca, Francesco</creatorcontrib><creatorcontrib>Pandini, Giuseppe</creatorcontrib><creatorcontrib>Sciacca, Laura</creatorcontrib><creatorcontrib>Vigneri, Riccardo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Endocrine reviews</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Belfiore, Antonino</au><au>Frasca, Francesco</au><au>Pandini, Giuseppe</au><au>Sciacca, Laura</au><au>Vigneri, Riccardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease</atitle><jtitle>Endocrine reviews</jtitle><addtitle>Endocr Rev</addtitle><date>2009-10</date><risdate>2009</risdate><volume>30</volume><issue>6</issue><spage>586</spage><epage>623</epage><pages>586-623</pages><issn>0163-769X</issn><eissn>1945-7189</eissn><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.
Recent insights indicate that insulin receptor isoform A or B expression influences metabolic and non-metabolic effects of insulin and insulin-like growth factors in target tissues.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>19752219</pmid><doi>10.1210/er.2008-0047</doi><tpages>38</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Alternative Splicing Animals Beta cells Cancer Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - metabolism Embryogenesis Embryonic growth stage Fetuses Growth and Development Growth factors Humans Hybrids Hyperinsulinemia Insulin Insulin receptors Insulin resistance Insulin-like growth factor I receptors Insulin-like growth factor II Insulin-Like Growth Factor II - metabolism Insulin-like growth factors Isoforms Molecular Structure Myotonic Dystrophy - metabolism Neoplasms - metabolism Neoplasms - therapy Physiology Protein Isoforms - metabolism Receptor, Insulin - chemistry Receptor, Insulin - genetics Receptor, Insulin - metabolism Receptor, Insulin - physiology Receptors Receptors, Somatomedin - metabolism Signal Transduction |
title | Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease |
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