Fiche publication
Date publication
février 2017
Journal
Diabetes
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BENANI Alexandre
Tous les auteurs :
Chrétien C, Fenech C, Liénard F, Grall S, Chevalier C, Chaudy S, Brenachot X, Berges R, Louche K, Stark R, Nédélec E, Laderrière A, Andrews ZB, Benani A, Flockerzi V, Gascuel J, Hartmann J, Moro C, Birnbaumer L, Leloup C, Pénicaud L, Fioramonti X
Lien Pubmed
Résumé
The mediobasal hypothalamus (MBH) contains neurons capable of directly detecting metabolic signals such as glucose to control energy homeostasis. Among them, glucose-excited (GE) neurons increase their electrical activity when glucose rises. In view of previous work, we hypothesized that transient receptor potential canonical type 3 (TRPC3) channels are involved in hypothalamic glucose detection and the control of energy homeostasis. To investigate the role of TRPC3, we used constitutive and conditional TRPC3-deficient mouse models. Hypothalamic glucose detection was studied in vivo by measuring food intake and insulin secretion in response to increased brain glucose level. The role of TRPC3 in GE neuron response to glucose was studied by using in vitro calcium imaging on freshly dissociated MBH neurons. We found that whole-body and MBH TRPC3-deficient mice have increased body weight and food intake. The anorectic effect of intracerebroventricular glucose and the insulin secretory response to intracarotid glucose injection are blunted in TRPC3-deficient mice. TRPC3 loss of function or pharmacological inhibition blunts calcium responses to glucose in MBH neurons in vitro. Together, the results demonstrate that TRPC3 channels are required for the response to glucose of MBH GE neurons and the central effect of glucose on insulin secretion and food intake.
Mots clés
Animals, Blotting, Western, Body Weight, genetics, Eating, genetics, Energy Metabolism, genetics, Fasting, Glucose, metabolism, Glucose Tolerance Test, Homeostasis, Hypothalamus, cytology, Insulin, metabolism, Insulin Secretion, Male, Mice, Mice, Inbred C57BL, Neurons, metabolism, Rats, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, TRPC Cation Channels, genetics
Référence
Diabetes. 2017 02;66(2):314-324
