Neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

Prévost, Gaëtan; Arabo, Arnaud; Solliec, Marie-Anne Le; Bons, J.; Picot, Marie Christine; Maucotel, Julie; Berrahmoune, Hind; Mehdi, Mouna El; Cherifi, Saloua; Bénani, Alexandre; Nédélec, Emmanuelle; Coëffier, Moı̈se; Leprince, Jérôme; Nordqvist, Anneli; Brunel, Valéry; Déchelotte, Pierre; Lefebvre, Henri; Anouar, Youssef; Chartrel, Nicolas

doi:10.1152/ajpendo.00540.2018

Cited by 14 publications

(31 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Altogether, these findings reveal that depletion of 26RFa induces an alteration of glucose homeostasis that is due to a defect in insulin secretion but not in insulin sensitivity. Consistent with this finding, we have previously shown that 26RFa stimulates insulin secretion by the pancreatic β cells (24) and that administration of a 26RFa receptor antagonist alters the anti-hyperglycemic response of the organism to a glucose challenge (28). Collectively, these data confirm that 26RFa is an important regulator of glucose homeostasis.…”

Section: Discussionsupporting

confidence: 67%

“…Accumulated data obtained during the last decade have promoted the evidence that the neuropeptide 26RFa plays a key role in the control of feeding behaviour (10, 13, 14) and the regulation of glucose homeostasis (24, 25, 27, 28). Supporting this notion, it has been recently shown that acute administration of a GPR103 (the 26RFa receptor) antagonist decreases food intake (30) and reduces the global glucose-induced incretin effect as well as the insulin sensitivity (28). However, chronic deficiency of 26RFa signalling on energy and glucose homeostasis remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA from livers of mice was isolated as previously described (28). Relative expression of the glucose 6 phosphatase (G6PC), glucokinase (GCK) and phosphoenolpyruvate carboxykinase 1 (PCK1) genes was quantified by real-time PCR with appropriate primers (Table 1).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Mehdi

Takhlidjt

Khiar

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

1 Introduction: 26RFa (QRFP) is a biologically active peptide that has been found to control 2 feeding behaviour by stimulating food intake, and to regulate glucose homeostasis by acting as 3 an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene 4 knockout on the regulation of energy and glucose metabolism. 5Research design and methods: 26RFa mutant mice were generated by homologous 6 recombination, in which the entire coding region of prepro-26RFa was replaced by the iCre 7 sequence. Energy and glucose metabolism was evaluated through measurement of 8 complementary parameters. Morphological and physiological alterations of the pancreatic islets 9 were also investigated. 10Results: Our data do not reveal significant alteration of energy metabolism in the 26RFa-11 deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa 12 mutant mice exhibit an altered glycemic phenotype with an increased hyperglycemia after a 13 glucose challenge associated with an impaired insulin production, and an elevated hepatic 14 glucose production. 2D and 3D immunohistochemical experiments indicate that the insulin 15 content of pancreatic β cells is much lower in the 26RFa -/mice as compared to the wild-type 16 littermates. 17Conclusion: Disruption of the 26RFa gene induces substantial alteration in the regulation of 18 glucose homeostasis with, in particular, a deficit in insulin production by the pancreatic islets. 19These findings further support the notion that 26RFa is an important regulator of glucose 20 homeostasis. 21 22

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Mehdi

Takhlidjt

Khiar

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Finally, we reported that an oral glucose challenge induces a massive secretion of 26RFa by the gut into the blood, strongly suggesting that this neuropeptide regulates glycemia by acting as an incretin 24. This incretin effect of 26RFa has been very recently confirmed by the observation that administration of a GPR103 antagonist reduces the global glucose-induced incretin effect, and also decreases insulin sensitivity 28…”

Section: Introductionmentioning

confidence: 77%

“…Total RNA from livers of mice was isolated as previously described 28. Relative expression of glucose 6 phosphatase (G6PC), glucokinase (GCK) and phosphoenolpyruvate carboxykinase 1 (PCK1) genes was quantified by real-time PCR with appropriate primers (table 1).…”

Section: Methodsmentioning

confidence: 99%

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

El-Mehdi

Takhlidjt

Khiar

et al. 2020

BMJ Open Diab Res Care

Self Cite

View full text Add to dashboard Cite

Significance of this studyWhat is already known about this subject? ► 26RFa is a biologically active peptide produced in abundance in the gut and the pancreas. ► 26RFa has been found to regulate glucose homeostasis by acting as an incretin and by increasing insulin sensitivity.What are the new findings?► 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, assessing therefore the notion that 26RFa is an important regulator of glucose homeostasis.How might these results change the focus of research or clinical practice?► Identification of a novel actor in the regulation of glucose homeostasis is crucial to better understand the general control of glucose metabolism in physiological and pathophysiological conditions, and opens new fields of investigation to develop innovative drugs to treat diabetes mellitus. AbStrActIntroduction 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.

show abstract

The 26RFa (QRFP)/GPR103 neuropeptidergic system in mice relays insulin signalling into the brain to regulate glucose homeostasis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis 26RFa (pyroglutamilated RFamide peptide [QRFP]) is a biologically active peptide that regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity at the periphery. 26RFa is also produced by a neuronal population localised in the hypothalamus. In this study we investigated whether 26RFa neurons are involved in the hypothalamic regulation of glucose homeostasis. Methods 26Rfa +/+ , 26Rfa -/and insulin-deficient male C57Bl/6J mice were used in this study. Mice received an acute intracerebroventricular (i.c.v.) injection of 26RFa, insulin or the 26RFa receptor (GPR103) antagonist 25e and were subjected to IPGTTs, insulin tolerance tests, acute glucose-stimulated insulin secretion tests and pyruvate tolerance tests (PTTs). Secretion of 26RFa by hypothalamic explants after incubation with glucose, leptin or insulin was assessed. Expression and quantification of the genes encoding 26RFa, agouti-related protein, the insulin receptor and GPR103 were evaluated by quantitative reverse transcription PCR and RNAscope in situ hybridisation. Results Our data indicate that i.c.v.-injected 26RFa induces a robust antihyperglycaemic effect associated with an increase in insulin production by the pancreatic islets. In addition, we found that insulin strongly stimulates 26Rfa expression and secretion by the hypothalamus. RNAscope experiments revealed that neurons expressing 26Rfa are mainly localised in the lateral hypothalamic area, that they co-express the gene encoding the insulin receptor and that insulin induces the expression of 26Rfa in these neurons. Concurrently, the central antihyperglycaemic effect of insulin is abolished in the presence of a GPR103 antagonist and in 26RFa-deficient mice. Finally, our data indicate that the hypothalamic 26RFa neurons are not involved in the central inhibitory effect of insulin on hepatic glucose production, but mediate the central effects of the hormone on its own peripheral production. Conclusion/interpretationWe have identified a novel mechanism in the hypothalamic regulation of glucose homeostasis, the 26RFa/GPR103 system, and we provide evidence that this neuronal peptidergic system is a key relay for the central regulation of glucose metabolism by insulin.

show abstract

Neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

Cited by 14 publications

References 33 publications

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

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

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

The 26RFa (QRFP)/GPR103 neuropeptidergic system in mice relays insulin signalling into the brain to regulate glucose homeostasis

Contact Info

Product

Resources

About