title: Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout.
abstract: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been implicated in the control of blood glucose by its potent effect on expression and signaling of various nuclear receptors. To understand the role of COUP-TFII in glucose homeostasis, conditional COUP-TFII-deficient mice were generated and crossed with mice expressing Cre under the control of rat insulin II gene promoter, resulting in deletion of COUP-TFII in pancreatic beta-cells. Homozygous mutants died before birth for yet undetermined reasons. Heterozygous mice appeared healthy at birth and showed normal growth and fertility. When challenged intraperitoneally, the animals had glucose intolerance associated with reduced glucose-stimulated insulin secretion. Moreover, these heterozygous mice presented a mild increase in fasting and random-fed circulating insulin levels. In accordance, islets isolated from these animals exhibited higher insulin secretion in low glucose conditions and markedly decreased glucose-stimulated insulin secretion. Their pancreata presented normal microscopic architecture and insulin content up to 16 weeks of study. Altered insulin secretion was associated with peripheral insulin resistance in whole animals. It can be concluded that COUP-TFII is a new, important regulator of glucose homeostasis and insulin sensitivity.
authors.affiliation: Institut Cochin, U567/INSERM, UMR8104/Centre National de la Recherche Scientifique, Université René Descartes, Department GDPM, 24 rue du Faubourg Saint-Jacques 75014 Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Bardoux
authors.forename: Pili
authors.initials: P
authors.lastname: Zhang
authors.forename: Daisy
authors.initials: D
authors.lastname: Flamez
authors.forename: Anaïs
authors.initials: A
authors.lastname: Perilhou
authors.forename: Tiphaine Aguirre
authors.initials: TA
authors.lastname: Lavin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Tanti
authors.forename: Karine
authors.initials: K
authors.lastname: Hellemans
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gomas
authors.forename: Cécile
authors.initials: C
authors.lastname: Godard
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Andreelli
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Buccheri
authors.forename: Axel
authors.initials: A
authors.lastname: Kahn
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Marchand-Brustel
authors.forename: Rémy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Frans
authors.initials: F
authors.lastname: Schuit
authors.forename: Mireille
authors.initials: M
authors.lastname: Vasseur-Cognet
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D002645:Chickens; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D017353:Gene Deletion; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D011987:Receptors, Steroid / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D008055:Lipids; C497587:Nr2f2 protein, mouse; C497588:Nr2f2 protein, rat; D011987:Receptors, Steroid; D014157:Transcription Factors; D005934:Glucagon; D005947:Glucose