title: Hypothalamic ventromedial COUP-TFII protects against hypoglycemia-associated autonomic failure.
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.
authors: Institut National de la Santé et de la Recherche Médicale, Unité 1016, Institut Cochin, 75014 Paris, France.
authors: Lina
authors: L
authors: Sabra-Makke
authors: Micol
authors: M
authors: Maritan
authors: Julien
authors: J
authors: Planchais
authors: Marie
authors: M
authors: Boutant
authors: Jean-Paul
authors: JP
authors: Pégorier
authors: Patrick C
authors: PC
authors: Even
authors: Mireille
authors: M
authors: Vasseur-Cognet
authors: Pascale
authors: P
authors: Bossard
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051837:COUP Transcription Factor II / Q000096:biosynthesis* / Q000235:genetics; D002645:Chickens; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D007003:Hypoglycemia / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism* / Q000473:pathology
chemical_list: D051837:COUP Transcription Factor II; D009419:Nerve Tissue Proteins; D054339:Steroidogenic Factor 1; C515058:steroidogenic factor 1, mouse; D005947:Glucose