PT  - JOURNAL ARTICLE
AU  - Mouna El-Mehdi
AU  - Saloua Takhlidjt
AU  - Fayrouz Khiar
AU  - Gaëtan Prévost
AU  - Jean-Luc do Rego
AU  - Jean-Claude do Rego
AU  - Alexandre Benani
AU  - Emmanuelle Nedelec
AU  - David Godefroy
AU  - Aranaud Arabo
AU  - Benjamin Lefranc
AU  - Jérôme Leprince
AU  - Youssef Anouar
AU  - Nicolas Chartrel
AU  - Marie Picot
TI  - Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP)
AID  - 10.1136/bmjdrc-2019-000942
DP  - 2020 Feb 01
TA  - BMJ Open Diabetes Research & Care
PG  - e000942
VI  - 8
IP  - 1
4099  - http://drc.bmj.com/content/8/1/e000942.short
4100  - http://drc.bmj.com/content/8/1/e000942.full
SO  - BMJ Open Diab Res Care2020 Feb 01; 8
AB  - Introduction 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.Research design and methods 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.Results 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−/− mice as compared with the wild-type littermates.Conclusion 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.