Essential role of chicken ovalbumin upstream promoter-transcription factor II in insulin secretion and insulin sensitivity revealed by conditional gene knockout.
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.
Bardoux
Pascale
P
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.
Zhang
Pili
P
Flamez
Daisy
D
Perilhou
Anaïs
A
Lavin
Tiphaine Aguirre
TA
Tanti
Jean-François
JF
Hellemans
Karine
K
Gomas
Emmanuel
E
Godard
Cécile
C
Andreelli
Fabrizio
F
Buccheri
Maria Antonietta
MA
Kahn
Axel
A
Le Marchand-Brustel
Yannick
Y
Burcelin
Rémy
R
Schuit
Frans
F
Vasseur-Cognet
Mireille
M
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*
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