Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Accéder directement au contenu
Article Dans Une Revue Diabetes Année : 2010

Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation

Nicolas Marsollier
  • Fonction : Auteur
Zhentao Song
  • Fonction : Auteur
Kurt A. Fakira
  • Fonction : Auteur
Reema M. Patel
  • Fonction : Auteur
Stacey Brown
  • Fonction : Auteur
Thibaut Duparc
  • Fonction : Auteur
Arnaldo Pica-Mendez
  • Fonction : Auteur
Nicole M. Sanders
  • Fonction : Auteur
Claude Knauf
  • Fonction : Auteur
Philippe Valet
Rory J. Mccrimmon
  • Fonction : Auteur
Annie Beuve
  • Fonction : Auteur
Christophe Magnan
Vanessa H. Routh
  • Fonction : Auteur

Résumé

OBJECTIVE: The response of ventromedial hypothalamic (VMH) glucose-inhibited neurons to decreased glucose is impaired under conditions where the counterregulatory response (CRR) to hypoglycemia is impaired (e.g., recurrent hypoglycemia). This suggests a role for glucose-inhibited neurons in the CRR. We recently showed that decreased glucose increases nitric oxide (NO) production in cultured VMH glucose-inhibited neurons. These in vitro data led us to hypothesize that NO release from VMH glucose-inhibited neurons is critical for the CRR. RESEARCH DESIGN AND METHODS: The CRR was evaluated in rats and mice in response to acute insulin-induced hypoglycemia and hypoglycemic clamps after modulation of brain NO signaling. The glucose sensitivity of ventromedial nucleus glucose-inhibited neurons was also assessed. RESULTS: Hypoglycemia increased hypothalamic constitutive NO synthase (NOS) activity and neuronal NOS (nNOS) but not endothelial NOS (eNOS) phosphorylation in rats. Intracerebroventricular and VMH injection of the nonselective NOS inhibitor N(G)-monomethyl-l-arginine (l-NMMA) slowed the recovery to euglycemia after hypoglycemia. VMH l-NMMA injection also increased the glucose infusion rate (GIR) and decreased epinephrine secretion during hyperinsulinemic/hypoglycemic clamp in rats. The GIR required to maintain the hypoglycemic plateau was higher in nNOS knockout than wild-type or eNOS knockout mice. Finally, VMH glucose-inhibited neurons were virtually absent in nNOS knockout mice. CONCLUSIONS: We conclude that VMH NO production is necessary for glucose sensing in glucose-inhibited neurons and full generation of the CRR to hypoglycemia. These data suggest that potentiating NO signaling may improve the defective CRR resulting from recurrent hypoglycemia in patients using intensive insulin therapy.

Dates et versions

hal-00680413 , version 1 (19-03-2012)

Identifiants

Citer

Xavier Fioramonti, Nicolas Marsollier, Zhentao Song, Kurt A. Fakira, Reema M. Patel, et al.. Ventromedial hypothalamic nitric oxide production is necessary for hypoglycemia detection and counterregulation. Diabetes, 2010, 59 (2), pp.519-528. ⟨10.2337/db09-0421⟩. ⟨hal-00680413⟩
140 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More