Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP).


Journal

BMJ open diabetes research & care
ISSN: 2052-4897
Titre abrégé: BMJ Open Diabetes Res Care
Pays: England
ID NLM: 101641391

Informations de publication

Date de publication:
02 2020
Historique:
received: 09 10 2019
revised: 09 01 2020
accepted: 28 01 2020
entrez: 2 3 2020
pubmed: 3 3 2020
medline: 8 1 2021
Statut: ppublish

Résumé

26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism. 26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated. Our data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibited an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. Two-dimensional and three-dimensional immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa Disruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis, with in particular a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.

Identifiants

pubmed: 32114486
pii: 8/1/e000942
doi: 10.1136/bmjdrc-2019-000942
pmc: PMC7050347
pii:
doi:

Substances chimiques

Blood Glucose 0
Insulin 0
Neuropeptides 0
RFamide peptide 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

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Auteurs

Mouna El-Mehdi (M)

U1239, INSERM, Rouen, France.

Saloua Takhlidjt (S)

U1239, INSERM, Rouen, France.

Fayrouz Khiar (F)

U1239, INSERM, Rouen, France.

Gaëtan Prévost (G)

U1239, INSERM, Rouen, France.

Jean-Luc do Rego (JL)

SCAC, Normandy University, Rouen, France.

Jean-Claude do Rego (JC)

SCAC, Normandy University, Rouen, France.

Alexandre Benani (A)

UMR6265, CNRS, Dijon, France.

Emmanuelle Nedelec (E)

UMR6265, CNRS, Dijon, France.

David Godefroy (D)

U1239, INSERM, Rouen, France.

Aranaud Arabo (A)

U1239, INSERM, Rouen, France.

Benjamin Lefranc (B)

U1239, INSERM, Rouen, France.

Jérôme Leprince (J)

U1239, INSERM, Rouen, France.

Youssef Anouar (Y)

U1239, INSERM, Rouen, France.

Nicolas Chartrel (N)

U1239, INSERM, Rouen, France nicolas.chartrel@univ-rouen.fr.

Marie Picot (M)

U1239, INSERM, Rouen, France.

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Classifications MeSH