Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.
Identifieur interne : 001107 ( PubMed/Corpus ); précédent : 001106; suivant : 001108Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.
Auteurs : Chloé Chrétien ; Claire Fenech ; Fabienne Liénard ; Sylvie Grall ; Charlène Chevalier ; Sylvie Chaudy ; Xavier Brenachot ; Raymond Berges ; Katie Louche ; Romana Stark ; Emmanuelle Nédélec ; Amélie Laderrière ; Zane B. Andrews ; Alexandre Benani ; Veit Flockerzi ; Jean Gascuel ; Jana Hartmann ; Cédric Moro ; Lutz Birnbaumer ; Corinne Leloup ; Luc Pénicaud ; Xavier FioramontiSource :
- Diabetes [ 1939-327X ] ; 2017.
English descriptors
- KwdEn :
- Animals, Blotting, Western, Body Weight (genetics), Eating (genetics), Energy Metabolism (genetics), Fasting, Glucose (metabolism), Glucose Tolerance Test, Homeostasis, Hypothalamus (cytology), Hypothalamus (metabolism), Insulin (secretion), Male, Mice, Mice, Inbred C57BL, Neurons (metabolism), Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, TRPC Cation Channels (genetics), TRPC Cation Channels (metabolism).
- MESH :
- chemical , genetics : TRPC Cation Channels.
- chemical , metabolism : Glucose, TRPC Cation Channels.
- cytology : Hypothalamus.
- genetics : Body Weight, Eating, Energy Metabolism.
- metabolism : Hypothalamus, Neurons.
- chemical , secretion : Insulin.
- Animals, Blotting, Western, Fasting, Glucose Tolerance Test, Homeostasis, Male, Mice, Mice, Inbred C57BL, Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction.
Abstract
The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.
DOI: 10.2337/db16-1114
PubMed: 27899482
Links to Exploration step
pubmed:27899482Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.</title><author><name sortKey="Chretien, Chloe" sort="Chretien, Chloe" uniqKey="Chretien C" first="Chloé" last="Chrétien">Chloé Chrétien</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fenech, Claire" sort="Fenech, Claire" uniqKey="Fenech C" first="Claire" last="Fenech">Claire Fenech</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lienard, Fabienne" sort="Lienard, Fabienne" uniqKey="Lienard F" first="Fabienne" last="Liénard">Fabienne Liénard</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Grall, Sylvie" sort="Grall, Sylvie" uniqKey="Grall S" first="Sylvie" last="Grall">Sylvie Grall</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chevalier, Charlene" sort="Chevalier, Charlene" uniqKey="Chevalier C" first="Charlène" last="Chevalier">Charlène Chevalier</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chaudy, Sylvie" sort="Chaudy, Sylvie" uniqKey="Chaudy S" first="Sylvie" last="Chaudy">Sylvie Chaudy</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brenachot, Xavier" sort="Brenachot, Xavier" uniqKey="Brenachot X" first="Xavier" last="Brenachot">Xavier Brenachot</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Berges, Raymond" sort="Berges, Raymond" uniqKey="Berges R" first="Raymond" last="Berges">Raymond Berges</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Louche, Katie" sort="Louche, Katie" uniqKey="Louche K" first="Katie" last="Louche">Katie Louche</name><affiliation><nlm:affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Stark, Romana" sort="Stark, Romana" uniqKey="Stark R" first="Romana" last="Stark">Romana Stark</name><affiliation><nlm:affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Nedelec, Emmanuelle" sort="Nedelec, Emmanuelle" uniqKey="Nedelec E" first="Emmanuelle" last="Nédélec">Emmanuelle Nédélec</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Laderriere, Amelie" sort="Laderriere, Amelie" uniqKey="Laderriere A" first="Amélie" last="Laderrière">Amélie Laderrière</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Andrews, Zane B" sort="Andrews, Zane B" uniqKey="Andrews Z" first="Zane B" last="Andrews">Zane B. Andrews</name><affiliation><nlm:affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Benani, Alexandre" sort="Benani, Alexandre" uniqKey="Benani A" first="Alexandre" last="Benani">Alexandre Benani</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Flockerzi, Veit" sort="Flockerzi, Veit" uniqKey="Flockerzi V" first="Veit" last="Flockerzi">Veit Flockerzi</name><affiliation><nlm:affiliation>Experimental and Clinical Pharmacology and Toxicology, Saarland University School of Medicine, Homburg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Gascuel, Jean" sort="Gascuel, Jean" uniqKey="Gascuel J" first="Jean" last="Gascuel">Jean Gascuel</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Hartmann, Jana" sort="Hartmann, Jana" uniqKey="Hartmann J" first="Jana" last="Hartmann">Jana Hartmann</name><affiliation><nlm:affiliation>Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Moro, Cedric" sort="Moro, Cedric" uniqKey="Moro C" first="Cédric" last="Moro">Cédric Moro</name><affiliation><nlm:affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Birnbaumer, Lutz" sort="Birnbaumer, Lutz" uniqKey="Birnbaumer L" first="Lutz" last="Birnbaumer">Lutz Birnbaumer</name><affiliation><nlm:affiliation>Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC.</nlm:affiliation></affiliation></author><author><name sortKey="Leloup, Corinne" sort="Leloup, Corinne" uniqKey="Leloup C" first="Corinne" last="Leloup">Corinne Leloup</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Penicaud, Luc" sort="Penicaud, Luc" uniqKey="Penicaud L" first="Luc" last="Pénicaud">Luc Pénicaud</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fioramonti, Xavier" sort="Fioramonti, Xavier" uniqKey="Fioramonti X" first="Xavier" last="Fioramonti">Xavier Fioramonti</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France xavier.fioramonti@inra.fr.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:27899482</idno><idno type="pmid">27899482</idno><idno type="doi">10.2337/db16-1114</idno><idno type="wicri:Area/PubMed/Corpus">001107</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001107</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.</title><author><name sortKey="Chretien, Chloe" sort="Chretien, Chloe" uniqKey="Chretien C" first="Chloé" last="Chrétien">Chloé Chrétien</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fenech, Claire" sort="Fenech, Claire" uniqKey="Fenech C" first="Claire" last="Fenech">Claire Fenech</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lienard, Fabienne" sort="Lienard, Fabienne" uniqKey="Lienard F" first="Fabienne" last="Liénard">Fabienne Liénard</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Grall, Sylvie" sort="Grall, Sylvie" uniqKey="Grall S" first="Sylvie" last="Grall">Sylvie Grall</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chevalier, Charlene" sort="Chevalier, Charlene" uniqKey="Chevalier C" first="Charlène" last="Chevalier">Charlène Chevalier</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chaudy, Sylvie" sort="Chaudy, Sylvie" uniqKey="Chaudy S" first="Sylvie" last="Chaudy">Sylvie Chaudy</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Brenachot, Xavier" sort="Brenachot, Xavier" uniqKey="Brenachot X" first="Xavier" last="Brenachot">Xavier Brenachot</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Berges, Raymond" sort="Berges, Raymond" uniqKey="Berges R" first="Raymond" last="Berges">Raymond Berges</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Louche, Katie" sort="Louche, Katie" uniqKey="Louche K" first="Katie" last="Louche">Katie Louche</name><affiliation><nlm:affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Stark, Romana" sort="Stark, Romana" uniqKey="Stark R" first="Romana" last="Stark">Romana Stark</name><affiliation><nlm:affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Nedelec, Emmanuelle" sort="Nedelec, Emmanuelle" uniqKey="Nedelec E" first="Emmanuelle" last="Nédélec">Emmanuelle Nédélec</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Laderriere, Amelie" sort="Laderriere, Amelie" uniqKey="Laderriere A" first="Amélie" last="Laderrière">Amélie Laderrière</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Andrews, Zane B" sort="Andrews, Zane B" uniqKey="Andrews Z" first="Zane B" last="Andrews">Zane B. Andrews</name><affiliation><nlm:affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Benani, Alexandre" sort="Benani, Alexandre" uniqKey="Benani A" first="Alexandre" last="Benani">Alexandre Benani</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Flockerzi, Veit" sort="Flockerzi, Veit" uniqKey="Flockerzi V" first="Veit" last="Flockerzi">Veit Flockerzi</name><affiliation><nlm:affiliation>Experimental and Clinical Pharmacology and Toxicology, Saarland University School of Medicine, Homburg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Gascuel, Jean" sort="Gascuel, Jean" uniqKey="Gascuel J" first="Jean" last="Gascuel">Jean Gascuel</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Hartmann, Jana" sort="Hartmann, Jana" uniqKey="Hartmann J" first="Jana" last="Hartmann">Jana Hartmann</name><affiliation><nlm:affiliation>Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Moro, Cedric" sort="Moro, Cedric" uniqKey="Moro C" first="Cédric" last="Moro">Cédric Moro</name><affiliation><nlm:affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</nlm:affiliation></affiliation></author><author><name sortKey="Birnbaumer, Lutz" sort="Birnbaumer, Lutz" uniqKey="Birnbaumer L" first="Lutz" last="Birnbaumer">Lutz Birnbaumer</name><affiliation><nlm:affiliation>Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC.</nlm:affiliation></affiliation></author><author><name sortKey="Leloup, Corinne" sort="Leloup, Corinne" uniqKey="Leloup C" first="Corinne" last="Leloup">Corinne Leloup</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Penicaud, Luc" sort="Penicaud, Luc" uniqKey="Penicaud L" first="Luc" last="Pénicaud">Luc Pénicaud</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</nlm:affiliation></affiliation></author><author><name sortKey="Fioramonti, Xavier" sort="Fioramonti, Xavier" uniqKey="Fioramonti X" first="Xavier" last="Fioramonti">Xavier Fioramonti</name><affiliation><nlm:affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France xavier.fioramonti@inra.fr.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Diabetes</title><idno type="eISSN">1939-327X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Body Weight (genetics)</term><term>Eating (genetics)</term><term>Energy Metabolism (genetics)</term><term>Fasting</term><term>Glucose (metabolism)</term><term>Glucose Tolerance Test</term><term>Homeostasis</term><term>Hypothalamus (cytology)</term><term>Hypothalamus (metabolism)</term><term>Insulin (secretion)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neurons (metabolism)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Real-Time Polymerase Chain Reaction</term><term>TRPC Cation Channels (genetics)</term><term>TRPC Cation Channels (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>TRPC Cation Channels</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Glucose</term><term>TRPC Cation Channels</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Hypothalamus</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Body Weight</term><term>Eating</term><term>Energy Metabolism</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hypothalamus</term><term>Neurons</term></keywords><keywords scheme="MESH" type="chemical" qualifier="secretion" xml:lang="en"><term>Insulin</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Blotting, Western</term><term>Fasting</term><term>Glucose Tolerance Test</term><term>Homeostasis</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Real-Time Polymerase Chain Reaction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">27899482</PMID><DateCreated><Year>2016</Year><Month>11</Month><Day>30</Day></DateCreated><DateCompleted><Year>2017</Year><Month>06</Month><Day>05</Day></DateCompleted><DateRevised><Year>2017</Year><Month>06</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1939-327X</ISSN><JournalIssue CitedMedium="Internet"><Volume>66</Volume><Issue>2</Issue><PubDate><Year>2017</Year><Month>Feb</Month></PubDate></JournalIssue><Title>Diabetes</Title><ISOAbbreviation>Diabetes</ISOAbbreviation></Journal><ArticleTitle>Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis.</ArticleTitle><Pagination><MedlinePgn>314-324</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.2337/db16-1114</ELocationID><Abstract><AbstractText>The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.</AbstractText><CopyrightInformation>© 2017 by the American Diabetes Association.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chrétien</LastName><ForeName>Chloé</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fenech</LastName><ForeName>Claire</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liénard</LastName><ForeName>Fabienne</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Grall</LastName><ForeName>Sylvie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chevalier</LastName><ForeName>Charlène</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chaudy</LastName><ForeName>Sylvie</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brenachot</LastName><ForeName>Xavier</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Berges</LastName><ForeName>Raymond</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Louche</LastName><ForeName>Katie</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stark</LastName><ForeName>Romana</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nédélec</LastName><ForeName>Emmanuelle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Laderrière</LastName><ForeName>Amélie</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andrews</LastName><ForeName>Zane B</ForeName><Initials>ZB</Initials><AffiliationInfo><Affiliation>Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Department of Physiology, Monash University, Clayton, VIC, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benani</LastName><ForeName>Alexandre</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Flockerzi</LastName><ForeName>Veit</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Experimental and Clinical Pharmacology and Toxicology, Saarland University School of Medicine, Homburg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gascuel</LastName><ForeName>Jean</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hartmann</LastName><ForeName>Jana</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Institute of Neuroscience and Center for Integrated Protein Science, Technical University Munich, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moro</LastName><ForeName>Cédric</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>INSERM UMR1048, Institute of Metabolic and Cardiovascular Diseases, Obesity Research Laboratory, University of Toulouse, Toulouse, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Birnbaumer</LastName><ForeName>Lutz</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Neurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Biomedical Research, Catholic University of Argentina, Buenos Aires, Argentina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Leloup</LastName><ForeName>Corinne</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pénicaud</LastName><ForeName>Luc</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fioramonti</LastName><ForeName>Xavier</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Centre des Sciences du Goût et de l'Alimentation, CNRS, Institut National de la Recherche Agronomique, University of Bourgogne Franche-Comté, Dijon, France xavier.fioramonti@inra.fr.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2016</Year><Month>11</Month><Day>29</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Diabetes</MedlineTA><NlmUniqueID>0372763</NlmUniqueID><ISSNLinking>0012-1797</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007328">Insulin</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050052">TRPC Cation Channels</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C104603">TRPC3 cation channel</NameOfSubstance></Chemical><Chemical><RegistryNumber>IY9XDZ35W2</RegistryNumber><NameOfSubstance UI="D005947">Glucose</NameOfSubstance></Chemical></ChemicalList><CitationSubset>AIM</CitationSubset><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015153" 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MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D060888" MajorTopicYN="N">Real-Time Polymerase Chain Reaction</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D050052" MajorTopicYN="N">TRPC Cation Channels</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>09</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>11</Month><Day>17</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2016</Year><Month>12</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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