Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure
The nuclear receptor Chicken Ovalbumin Upstream Promoter–Transcription Factor II (COUP-TFII) is an important coordinator of glucose homeostasis through its function in different organs such as the endocrine pancreas, adipose tissue, skeletal muscle, and liver. Recently we have demonstrated that COUP...
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Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2013-03, Vol.110 (11), p.4333-4338 |
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creator | Sabra-Makke, Lina Maritan, Micol Planchais, Julien Boutant, Marie Pégorier, Jean-Paul Even, Patrick C. Vasseur-Cognet, Mireille Bossard, Pascale |
description | The nuclear receptor Chicken Ovalbumin Upstream Promoter–Transcription Factor II (COUP-TFII) is an important coordinator of glucose homeostasis through its function in different organs such as the endocrine pancreas, adipose tissue, skeletal muscle, and liver. Recently we have demonstrated that COUP-TFII expression in the hypothalamus is restricted to a subpopulation of neurons expressing the steroidogenic factor 1 transcription factor, known to play a crucial role in glucose homeostasis. To understand the functional significance of COUP-TFII expression in the steroidogenic factor 1 neurons, we generated hypothalamic ventromedial nucleus-specific COUP-TFII KO mice using the cyclization recombination/locus of X-overP1 technology. The heterozygous mutant mice display insulin hypersensitivity and a leaner phenotype associated with increased energy expenditure and similar food intake. These mutant mice also present a defective counterregulation to hypoglycemia with altered glucagon secretion. Moreover, the mutant mice are more likely to develop hypoglycemia-associated autonomic failure in response to recurrent hypoglycemic or glucopenic events. Therefore, COUP-TFII expression levels in the ventromedial nucleus are keys in the ability to resist the onset of hypoglycemia-associated autonomic failure. |
doi_str_mv | 10.1073/pnas.1219262110 |
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Recently we have demonstrated that COUP-TFII expression in the hypothalamus is restricted to a subpopulation of neurons expressing the steroidogenic factor 1 transcription factor, known to play a crucial role in glucose homeostasis. To understand the functional significance of COUP-TFII expression in the steroidogenic factor 1 neurons, we generated hypothalamic ventromedial nucleus-specific COUP-TFII KO mice using the cyclization recombination/locus of X-overP1 technology. The heterozygous mutant mice display insulin hypersensitivity and a leaner phenotype associated with increased energy expenditure and similar food intake. These mutant mice also present a defective counterregulation to hypoglycemia with altered glucagon secretion. Moreover, the mutant mice are more likely to develop hypoglycemia-associated autonomic failure in response to recurrent hypoglycemic or glucopenic events. Therefore, COUP-TFII expression levels in the ventromedial nucleus are keys in the ability to resist the onset of hypoglycemia-associated autonomic failure.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1219262110</identifier><identifier>PMID: 23440210</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Adipose tissue ; Agricultural sciences ; Animals ; Autonomic Nervous System Diseases - etiology ; Autonomic Nervous System Diseases - genetics ; Autonomic Nervous System Diseases - metabolism ; Autonomic Nervous System Diseases - pathology ; Biological Sciences ; Blood glucose ; Brain ; Chickens ; COUP Transcription Factor II - biosynthesis ; COUP Transcription Factor II - genetics ; Food intake ; Gene expression ; Glucose ; Glucose - genetics ; Glucose - metabolism ; Heterozygote ; Homeostasis ; Hypersensitivity ; Hypoglycemia ; Hypoglycemia - complications ; Hypoglycemia - genetics ; Hypoglycemia - metabolism ; Hypoglycemia - pathology ; Insulin ; Insulin resistance ; Life Sciences ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins - biosynthesis ; Nerve Tissue Proteins - genetics ; Neurons ; Neurons - metabolism ; Neurons - pathology ; Organ Specificity - genetics ; Phenotypes ; Secretion ; Steroidogenic Factor 1 - genetics ; Steroidogenic Factor 1 - metabolism ; Type 1 diabetes mellitus ; Ventromedial Hypothalamic Nucleus - metabolism ; Ventromedial Hypothalamic Nucleus - pathology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2013-03, Vol.110 (11), p.4333-4338</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Mar 12, 2013</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-a61843cfb5430ac83fd1fc20499fc1f5f9e8659f050d2ffea0fa89fdb7152e3e3</citedby><cites>FETCH-LOGICAL-c591t-a61843cfb5430ac83fd1fc20499fc1f5f9e8659f050d2ffea0fa89fdb7152e3e3</cites><orcidid>0000-0002-7302-1051 ; 0000-0001-5733-3023</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/110/11.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/42583249$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/42583249$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27929,27930,53796,53798,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23440210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01004468$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Sabra-Makke, Lina</creatorcontrib><creatorcontrib>Maritan, Micol</creatorcontrib><creatorcontrib>Planchais, Julien</creatorcontrib><creatorcontrib>Boutant, Marie</creatorcontrib><creatorcontrib>Pégorier, Jean-Paul</creatorcontrib><creatorcontrib>Even, Patrick C.</creatorcontrib><creatorcontrib>Vasseur-Cognet, Mireille</creatorcontrib><creatorcontrib>Bossard, Pascale</creatorcontrib><title>Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The nuclear receptor Chicken Ovalbumin Upstream Promoter–Transcription Factor II (COUP-TFII) is an important coordinator of glucose homeostasis through its function in different organs such as the endocrine pancreas, adipose tissue, skeletal muscle, and liver. Recently we have demonstrated that COUP-TFII expression in the hypothalamus is restricted to a subpopulation of neurons expressing the steroidogenic factor 1 transcription factor, known to play a crucial role in glucose homeostasis. To understand the functional significance of COUP-TFII expression in the steroidogenic factor 1 neurons, we generated hypothalamic ventromedial nucleus-specific COUP-TFII KO mice using the cyclization recombination/locus of X-overP1 technology. The heterozygous mutant mice display insulin hypersensitivity and a leaner phenotype associated with increased energy expenditure and similar food intake. These mutant mice also present a defective counterregulation to hypoglycemia with altered glucagon secretion. Moreover, the mutant mice are more likely to develop hypoglycemia-associated autonomic failure in response to recurrent hypoglycemic or glucopenic events. Therefore, COUP-TFII expression levels in the ventromedial nucleus are keys in the ability to resist the onset of hypoglycemia-associated autonomic failure.</description><subject>Adipose tissue</subject><subject>Agricultural sciences</subject><subject>Animals</subject><subject>Autonomic Nervous System Diseases - etiology</subject><subject>Autonomic Nervous System Diseases - genetics</subject><subject>Autonomic Nervous System Diseases - metabolism</subject><subject>Autonomic Nervous System Diseases - pathology</subject><subject>Biological Sciences</subject><subject>Blood glucose</subject><subject>Brain</subject><subject>Chickens</subject><subject>COUP Transcription Factor II - biosynthesis</subject><subject>COUP Transcription Factor II - genetics</subject><subject>Food intake</subject><subject>Gene expression</subject><subject>Glucose</subject><subject>Glucose - genetics</subject><subject>Glucose - metabolism</subject><subject>Heterozygote</subject><subject>Homeostasis</subject><subject>Hypersensitivity</subject><subject>Hypoglycemia</subject><subject>Hypoglycemia - complications</subject><subject>Hypoglycemia - genetics</subject><subject>Hypoglycemia - metabolism</subject><subject>Hypoglycemia - pathology</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Life Sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Nerve Tissue Proteins - biosynthesis</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Neurons</subject><subject>Neurons - metabolism</subject><subject>Neurons - pathology</subject><subject>Organ Specificity - genetics</subject><subject>Phenotypes</subject><subject>Secretion</subject><subject>Steroidogenic Factor 1 - genetics</subject><subject>Steroidogenic Factor 1 - metabolism</subject><subject>Type 1 diabetes mellitus</subject><subject>Ventromedial Hypothalamic Nucleus - metabolism</subject><subject>Ventromedial Hypothalamic Nucleus - pathology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc2LEzEYxgdR3Fo9e1IHvOhhdt83yWSSi7AU1xYKK7i9GtI0aadMJ91kptD_3gytXd1cAsnved6PJ8veI1wjVPRm3-p4jQQl4QQRXmQjBIkFZxJeZiMAUhWCEXaVvYlxCwCyFPA6uyKUMSAIo-z39Lj33UY3eleb_GDbLvidXdW6ySf3i5_Fw91slu-D76zpYq7Xum5jl2-SaN0cjd3VutAxelPrzq5y3Xe-9YOT03XTB_s2e-V0E-278z3OFnffHybTYn7_Yza5nRemlNgVmqNg1LhlyShoI6hboTMEmJTOoCudtIKX0kEJK-Kc1eC0kG61rLAkllo6zr6dfPf9MrVvhjl0o_ah3ulwVF7X6v-ftt6otT8oygEYlcng68lg80w2vZ2r4Q0wgYyLAyb2y7lY8I-9jZ3a1dHYptGt9X1USLFiIBjyhH5-hm59H9q0ioHiXKCsRKJuTpQJPsZg3aUDBDXkrIac1VPOSfHx33kv_N9gE_DpDAzKi93gh4rRdMbZhxOxjZ0PF4SRUlDC5JOD017pdaijWvwigGlhSDmnFf0D2wTB4g</recordid><startdate>20130312</startdate><enddate>20130312</enddate><creator>Sabra-Makke, Lina</creator><creator>Maritan, Micol</creator><creator>Planchais, Julien</creator><creator>Boutant, Marie</creator><creator>Pégorier, Jean-Paul</creator><creator>Even, Patrick C.</creator><creator>Vasseur-Cognet, Mireille</creator><creator>Bossard, Pascale</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7302-1051</orcidid><orcidid>https://orcid.org/0000-0001-5733-3023</orcidid></search><sort><creationdate>20130312</creationdate><title>Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure</title><author>Sabra-Makke, Lina ; Maritan, Micol ; Planchais, Julien ; Boutant, Marie ; Pégorier, Jean-Paul ; Even, Patrick C. ; Vasseur-Cognet, Mireille ; Bossard, Pascale</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c591t-a61843cfb5430ac83fd1fc20499fc1f5f9e8659f050d2ffea0fa89fdb7152e3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adipose tissue</topic><topic>Agricultural sciences</topic><topic>Animals</topic><topic>Autonomic Nervous System Diseases - etiology</topic><topic>Autonomic Nervous System Diseases - genetics</topic><topic>Autonomic Nervous System Diseases - metabolism</topic><topic>Autonomic Nervous System Diseases - pathology</topic><topic>Biological Sciences</topic><topic>Blood glucose</topic><topic>Brain</topic><topic>Chickens</topic><topic>COUP Transcription Factor II - biosynthesis</topic><topic>COUP Transcription Factor II - genetics</topic><topic>Food intake</topic><topic>Gene expression</topic><topic>Glucose</topic><topic>Glucose - genetics</topic><topic>Glucose - metabolism</topic><topic>Heterozygote</topic><topic>Homeostasis</topic><topic>Hypersensitivity</topic><topic>Hypoglycemia</topic><topic>Hypoglycemia - complications</topic><topic>Hypoglycemia - genetics</topic><topic>Hypoglycemia - metabolism</topic><topic>Hypoglycemia - pathology</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Life Sciences</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Nerve Tissue Proteins - biosynthesis</topic><topic>Nerve Tissue Proteins - 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sabra-Makke, Lina</au><au>Maritan, Micol</au><au>Planchais, Julien</au><au>Boutant, Marie</au><au>Pégorier, Jean-Paul</au><au>Even, Patrick C.</au><au>Vasseur-Cognet, Mireille</au><au>Bossard, Pascale</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2013-03-12</date><risdate>2013</risdate><volume>110</volume><issue>11</issue><spage>4333</spage><epage>4338</epage><pages>4333-4338</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>The nuclear receptor Chicken Ovalbumin Upstream Promoter–Transcription Factor II (COUP-TFII) is an important coordinator of glucose homeostasis through its function in different organs such as the endocrine pancreas, adipose tissue, skeletal muscle, and liver. Recently we have demonstrated that COUP-TFII expression in the hypothalamus is restricted to a subpopulation of neurons expressing the steroidogenic factor 1 transcription factor, known to play a crucial role in glucose homeostasis. To understand the functional significance of COUP-TFII expression in the steroidogenic factor 1 neurons, we generated hypothalamic ventromedial nucleus-specific COUP-TFII KO mice using the cyclization recombination/locus of X-overP1 technology. The heterozygous mutant mice display insulin hypersensitivity and a leaner phenotype associated with increased energy expenditure and similar food intake. These mutant mice also present a defective counterregulation to hypoglycemia with altered glucagon secretion. Moreover, the mutant mice are more likely to develop hypoglycemia-associated autonomic failure in response to recurrent hypoglycemic or glucopenic events. Therefore, COUP-TFII expression levels in the ventromedial nucleus are keys in the ability to resist the onset of hypoglycemia-associated autonomic failure.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>23440210</pmid><doi>10.1073/pnas.1219262110</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-7302-1051</orcidid><orcidid>https://orcid.org/0000-0001-5733-3023</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adipose tissue Agricultural sciences Animals Autonomic Nervous System Diseases - etiology Autonomic Nervous System Diseases - genetics Autonomic Nervous System Diseases - metabolism Autonomic Nervous System Diseases - pathology Biological Sciences Blood glucose Brain Chickens COUP Transcription Factor II - biosynthesis COUP Transcription Factor II - genetics Food intake Gene expression Glucose Glucose - genetics Glucose - metabolism Heterozygote Homeostasis Hypersensitivity Hypoglycemia Hypoglycemia - complications Hypoglycemia - genetics Hypoglycemia - metabolism Hypoglycemia - pathology Insulin Insulin resistance Life Sciences Mice Mice, Transgenic Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Neurons Neurons - metabolism Neurons - pathology Organ Specificity - genetics Phenotypes Secretion Steroidogenic Factor 1 - genetics Steroidogenic Factor 1 - metabolism Type 1 diabetes mellitus Ventromedial Hypothalamic Nucleus - metabolism Ventromedial Hypothalamic Nucleus - pathology |
title | Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure |
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