title: Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis.
abstract: 26RFa is a hypothalamic neuropeptide that promotes food intake. 26RFa is upregulated in obese animal models, and its orexigenic activity is accentuated in rodents fed a high-fat diet, suggesting that this neuropeptide might play a role in the development and maintenance of the obese status. As obesity is frequently associated with type 2 diabetes, we investigated whether 26RFa may be involved in the regulation of glucose homeostasis. In the current study, we show a moderate positive correlation between plasma 26RFa levels and plasma insulin in patients with diabetes. Plasma 26RFa concentration also increases in response to an oral glucose tolerance test. In addition, we found that 26RFa and its receptor GPR103 are present in human pancreatic β-cells as well as in the gut. In mice, 26RFa attenuates the hyperglycemia induced by a glucose load, potentiates insulin sensitivity, and increases plasma insulin concentrations. Consistent with these data, 26RFa stimulates insulin production by MIN6 insulinoma cells. Finally, we show, using in vivo and in vitro approaches, that a glucose load induces a massive secretion of 26RFa by the small intestine. Altogether, the present data indicate that 26RFa acts as an incretin to regulate glucose homeostasis.
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Department of Endocrinology, Diabetes and Metabolic Diseases, Institute for Research and Innovation in Biomedicine, University Hospital of Rouen, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Gaëtan
authors: G
authors: Prévost
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Lydie
authors: L
authors: Jeandel
authors: Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Arnaud
authors: A
authors: Arabo
authors: Normandy University, Caen, France University of Rouen, Rouen, France INSERM U1073, Institute for Research and Innovation in Biomedicine, Rouen, France Department of Nutrition, University Hospital of Rouen, Rouen, France.
authors: Moïse
authors: M
authors: Coëffier
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France Biological Engineering Laboratory, Life Sciences, Sultan Moulay Slimane University, Beni-Mellal, Morocco.
authors: Mariama
authors: M
authors: El Ouahli
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Marie
authors: M
authors: Picot
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: David
authors: D
authors: Alexandre
authors: Normandy University, Caen, France University of Rouen, Rouen, France Department of Pathology, University Hospital of Rouen, Rouen, France.
authors: Françoise
authors: F
authors: Gobet
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Jérôme
authors: J
authors: Leprince
authors: Department of Endocrinology, Diabetes and Metabolic Diseases, Institute for Research and Innovation in Biomedicine, University Hospital of Rouen, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Hind
authors: H
authors: Berrahmoune
authors: Normandy University, Caen, France University of Rouen, Rouen, France INSERM U1073, Institute for Research and Innovation in Biomedicine, Rouen, France Department of Nutrition, University Hospital of Rouen, Rouen, France.
authors: Pierre
authors: P
authors: Déchelotte
authors: Department of Cell Biology, Physiology, and Immunology, Instituto Maimónides de Investigación Biomédica de Córdoba/Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain.
authors: Maria
authors: M
authors: Malagon
authors: INSERM U859, Biotherapies of Diabetes, Faculty of Medicine, University of Lille, Lille, France.
authors: Caroline
authors: C
authors: Bonner
authors: INSERM U859, Biotherapies of Diabetes, Faculty of Medicine, University of Lille, Lille, France.
authors: Julie
authors: J
authors: Kerr-Conte
authors: Biological Engineering Laboratory, Life Sciences, Sultan Moulay Slimane University, Beni-Mellal, Morocco.
authors: Fatiha
authors: F
authors: Chigr
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Department of Endocrinology, Diabetes and Metabolic Diseases, Institute for Research and Innovation in Biomedicine, University Hospital of Rouen, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Hervé
authors: H
authors: Lefebvre
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France.
authors: Youssef
authors: Y
authors: Anouar
authors: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, Rouen, France Normandy University, Caen, France University of Rouen, Rouen, France nicolas.chartrel@univ-rouen.fr.
authors: Nicolas
authors: N
authors: Chartrel
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism*; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D051379:Mice; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism
chemical_list: D054795:Incretins; D007328:Insulin; D009479:Neuropeptides; C480638:prepro-26RFa protein, human; D005947:Glucose