Microarray analysis of genes with impaired insulin regulation in the skeletal muscle of type 2 diabetic patients indicates the involvement of basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2)
Identifieur interne : 000174 ( France/Analysis ); précédent : 000173; suivant : 000175Microarray analysis of genes with impaired insulin regulation in the skeletal muscle of type 2 diabetic patients indicates the involvement of basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2)
Auteurs : S. Rome [France] ; E. Meugnier [France] ; V. Lecomte [France] ; V. Berbe [France] ; J. Besson [France] ; C. Cerutti [France] ; S. Pesenti [France] ; A. Granjon [France] ; E. Disse [France] ; K. Clement [France] ; E. Lefai [France] ; M. Laville [France] ; H. Vidal [France]Source :
- Diabetologia [ 0012-186X ] ; 2009-09-01.
English descriptors
- KwdEn :
Abstract
Abstract: Aims/hypothesis: One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation. Thus, the identification of transcription factors affected by insulin in target tissues represents an important challenge. The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulin-regulated expression in human skeletal muscle. Methods: Using microarray analysis, we defined the sets of genes modulated during a 3 h hyperinsulinaemic–euglycaemic clamp (2 mU min−1 kg−1) in the skeletal muscle of insulin-sensitive control volunteers and in moderately obese insulin-resistant type 2 diabetic patients. Results: Of the 1,529 and 1,499 genes regulated during the clamp in control and diabetic volunteers, respectively, we identified 30 transcription factors with impaired insulin-regulation in type 2 diabetic patients. Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is strongly altered in the muscle of diabetic patients. Gene ontology analysis of BHLHB2 target genes, identified after BHLHB2 overexpression in human primary myotubes, demonstrated that about 10% of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor. The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle, including the regulation of a cluster of genes involved in muscle development and contraction. Conclusions/interpretation: We have identified BHLHB2 as a potential novel mediator of insulin transcriptional action in human skeletal muscle.
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DOI: 10.1007/s00125-009-1442-4
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Meugnier</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INRA 1235, INSERM 870, INSA-Lyon, Régulations Métaboliques Nutrition et Diabète, Université de Lyon, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation></author><author><name sortKey="Lecomte, V" sort="Lecomte, V" uniqKey="Lecomte V" first="V." last="Lecomte">V. 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Cerutti</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM ERI22/EA 4173, Biostatistiques, Université Lyon, 69008, Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Pesenti, S" sort="Pesenti, S" uniqKey="Pesenti S" first="S." last="Pesenti">S. 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Granjon</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INRA 1235, INSERM 870, INSA-Lyon, Régulations Métaboliques Nutrition et Diabète, Université de Lyon, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation></author><author><name sortKey="Disse, E" sort="Disse, E" uniqKey="Disse E" first="E." last="Disse">E. Disse</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hospices Civils de Lyon, Service de Diabétologie et Nutrition, Hôpital Edouard-Herriot, 69008, Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Clement, K" sort="Clement, K" uniqKey="Clement K" first="K." last="Clement">K. Clement</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Département Nutrition-Métabolisme-Différenciation, INSERM 872, Centre de Recherche des Cordeliers, 75006, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Lefai, E" sort="Lefai, E" uniqKey="Lefai E" first="E." last="Lefai">E. Lefai</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INRA 1235, INSERM 870, INSA-Lyon, Régulations Métaboliques Nutrition et Diabète, Université de Lyon, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation></author><author><name sortKey="Laville, M" sort="Laville, M" uniqKey="Laville M" first="M." last="Laville">M. Laville</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Hospices Civils de Lyon, Service de Diabétologie et Nutrition, Hôpital Edouard-Herriot, 69008, Lyon</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Centre de Recherche en Nutrition Humaine Rhône-Alpes, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation></author><author><name sortKey="Vidal, H" sort="Vidal, H" uniqKey="Vidal H" first="H." last="Vidal">H. Vidal</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INRA 1235, INSERM 870, INSA-Lyon, Régulations Métaboliques Nutrition et Diabète, Université de Lyon, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Centre de Recherche en Nutrition Humaine Rhône-Alpes, 69600, Oullins</wicri:regionArea><placeName><region type="region" nuts="2">Auvergne-Rhône-Alpes</region><region type="old region" nuts="2">Rhône-Alpes</region><settlement type="city">Oullins</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Diabetologia</title><title level="j" type="sub">Clinical and Experimental Diabetes and Metabolism</title><title level="j" type="abbrev">Diabetologia</title><idno type="ISSN">0012-186X</idno><idno type="eISSN">1432-0428</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2009-09-01">2009-09-01</date><biblScope unit="volume">52</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1899">1899</biblScope><biblScope unit="page" to="1912">1912</biblScope></imprint><idno type="ISSN">0012-186X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0012-186X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>BHLHB2</term><term>Hyperinsulinaemic–euglycaemic clamp</term><term>Insulin</term><term>Skeletal muscle</term><term>Transcription factors</term><term>Transcription network</term><term>Type 2 diabetes</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Aims/hypothesis: One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation. Thus, the identification of transcription factors affected by insulin in target tissues represents an important challenge. The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulin-regulated expression in human skeletal muscle. Methods: Using microarray analysis, we defined the sets of genes modulated during a 3 h hyperinsulinaemic–euglycaemic clamp (2 mU min−1 kg−1) in the skeletal muscle of insulin-sensitive control volunteers and in moderately obese insulin-resistant type 2 diabetic patients. Results: Of the 1,529 and 1,499 genes regulated during the clamp in control and diabetic volunteers, respectively, we identified 30 transcription factors with impaired insulin-regulation in type 2 diabetic patients. Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helix-loop-helix domain-containing, class B, 2 protein (BHLHB2), insulin regulation of which is strongly altered in the muscle of diabetic patients. Gene ontology analysis of BHLHB2 target genes, identified after BHLHB2 overexpression in human primary myotubes, demonstrated that about 10% of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor. The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle, including the regulation of a cluster of genes involved in muscle development and contraction. Conclusions/interpretation: We have identified BHLHB2 as a potential novel mediator of insulin transcriptional action in human skeletal muscle.</div></front></TEI><affiliations><list><country><li>France</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Rhône-Alpes</li><li>Île-de-France</li></region><settlement><li>Lyon</li><li>Oullins</li><li>Paris</li></settlement></list><tree><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Rome, S" sort="Rome, S" uniqKey="Rome S" first="S." last="Rome">S. Rome</name></region><name sortKey="Berbe, V" sort="Berbe, V" uniqKey="Berbe V" first="V." last="Berbe">V. Berbe</name><name sortKey="Besson, J" sort="Besson, J" uniqKey="Besson J" first="J." last="Besson">J. Besson</name><name sortKey="Cerutti, C" sort="Cerutti, C" uniqKey="Cerutti C" first="C." last="Cerutti">C. Cerutti</name><name sortKey="Clement, K" sort="Clement, K" uniqKey="Clement K" first="K." last="Clement">K. Clement</name><name sortKey="Disse, E" sort="Disse, E" uniqKey="Disse E" first="E." last="Disse">E. Disse</name><name sortKey="Granjon, A" sort="Granjon, A" uniqKey="Granjon A" first="A." last="Granjon">A. Granjon</name><name sortKey="Laville, M" sort="Laville, M" uniqKey="Laville M" first="M." last="Laville">M. Laville</name><name sortKey="Laville, M" sort="Laville, M" uniqKey="Laville M" first="M." last="Laville">M. Laville</name><name sortKey="Lecomte, V" sort="Lecomte, V" uniqKey="Lecomte V" first="V." last="Lecomte">V. Lecomte</name><name sortKey="Lefai, E" sort="Lefai, E" uniqKey="Lefai E" first="E." last="Lefai">E. Lefai</name><name sortKey="Meugnier, E" sort="Meugnier, E" uniqKey="Meugnier E" first="E." last="Meugnier">E. Meugnier</name><name sortKey="Pesenti, S" sort="Pesenti, S" uniqKey="Pesenti S" first="S." last="Pesenti">S. Pesenti</name><name sortKey="Rome, S" sort="Rome, S" uniqKey="Rome S" first="S." last="Rome">S. Rome</name><name sortKey="Vidal, H" sort="Vidal, H" uniqKey="Vidal H" first="H." last="Vidal">H. Vidal</name><name sortKey="Vidal, H" sort="Vidal, H" uniqKey="Vidal H" first="H." last="Vidal">H. Vidal</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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