26RFa, a novel orexigenic neuropeptide, inhibits insulin secretion in the rat pancreas

Egido, Eva M.; Hernández, Raquel; Leprince, Jérôme; Chartrel, Nicolas; Vaudry, Hubert; Marco, José; Silvestre, Ramona A.

doi:10.1016/j.peptides.2006.04.004

Cited by 45 publications

(55 citation statements)

References 34 publications

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“…Consistent with this finding, it has been recently reported that 43RFa, the N-extended form of 26RFa, stimulates insulin secretion by human pancreatic islets and INS-1E b-cells and that this effect is exerted via GPR103 (30). However, in the same study, the authors report that 26RFa inhibits insulin secretion via a signaling pathway distinct from GPR103, an observation previously made in rat perfused pancreas (31), and suggest that NPFF2 may mediate the insulinostatic activity of 26RFa. Here, we show that MIN6 cells do not express NPFF2, which might explain the discrepancy between our data and those found in INS-1 cells.…”

Section: Discussionsupporting

confidence: 71%

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis

et al. 2015

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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 highfat 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 b-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.26RFa and its N-extended form 43RFa (also referred to as QRFPs) are RFamide peptides discovered in the brain of various vertebrate species and identified as the cognate ligands of the human orphan G-protein-coupled receptor GPR103 (1-6). Neuroanatomical observations revealed that 26RFa-and GPR103-expressing neurons are primarily localized in hypothalamic nuclei involved in the control of feeding behavior (1,2,5,7). Indeed, intracerebroventricular administration of 26RFa or 43RFa stimulates food intake (1,5,8,9), and the neuropeptide exerts its orexigenic activity by modulating the neuropeptide Y/proopiomelanocortin system in the arcuate nucleus (9). Chronic injection of 43RFa induces a significant increase in mice body weight and fat mass, which is associated with a hyperphagic behavior (8), and the orexigenic activities of 26RFa and 43RFa are more robust in rodents fed a high-fat diet (8,10). Consistent with these observations, expression of prepro26RFa mRNA is upregulated in the hypothalamus of genetically obese ob/ob and db/db mice and rodents subjected to a high-fat diet (5,10). Altogether, these observations support the notion that 26RFa could play a role in the development and maintenance of the obese status.Obesity is frequently associated with type 2 diabetes, which is characterized by chronic hyperglycemia induced by impaired insulin secretion and increased insulin resistance (11-13). Accumulating evidence supports the

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Section: Discussionsupporting

confidence: 71%

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis

et al. 2015

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“…It should be mentioned that, in our perfused pancreas system, the same batch of PTX has been shown to be effective in preventing the inhibition of exendin-4-induced insulin secretion elicited by other insulinostatic peptides, such as 26RFa (Egido et al 2007) or ghrelin (unpublished data).…”

Section: Meansgsemmentioning

confidence: 79%

“…38 nM) reported for binding of kisspeptin-13 to rat GPR54 (Kotani et al 2001). The inhibition of insulin secretion by kisspeptin-13 in the nanomolar range resembles the effect induced by other insulinostatic peptides -galanin (Sharp et al 1989, Drews et al 1994, somatostatin (Schuit et al 1989), and 26RFa (Egido et al 2007). …”

Section: Meansgsemmentioning

confidence: 88%

“…3 days before perfusions. This PTX treatment has been found to effectively ADP-rybosylate and inactivate G i -protein coupled to adenylate cyclase (Ui et al 1984, Komatsu et al 1994, Silvestre et al 1994, Egido et al 2007. Control rats were subjected to a sham treatment consisting of injection of the corresponding buffer (50% glycerol, 0 .…”

Section: Pertussis Toxin Treatmentmentioning

confidence: 99%

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Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas

Silvestre

Egido²,

Hernández³

et al. 2007

Journal of Endocrinology

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Kisspeptins are a family of peptides encoded by the KISS1 gene, which binds to G-protein-coupled receptor (GPR54), an orphan GPR54 related to galanin receptors. Endogenous forms composed of 54, 14, and 13 amino acids have been identified. Kisspeptin and GPR54 mRNAs have been detected in pancreatic B and A cells. Furthermore, kisspeptin-54 has been shown to slightly stimulate the last phase of glucose-induced insulin secretion in mouse and human islets and to inhibit insulin release in MIN6 cells. We have investigated the effect of kisspeptin-13 on insulin, glucagon, and somatostatin secretion. The study was performed in the perfused rat pancreas. Glucose, arginine, carbachol, and exendin-4 were used as secretagogues. Hormones were measured by RIA. Kisspeptin-13 reduced glucose-induced insulin secretion in a dose-dependent manner (IC 50 Z1 . 2 nM) and inhibited the insulin responses to both carbachol and exendin-4. Kisspeptin-13 blocked arginine-induced insulin secretion without affecting the glucagon or somatostatin responses to this amino acid, thus indicating that kisspeptin-13 influences B cells directly, rather than through an A-or D-cell paracrine effect. The reduction of the insulin response to exendin-4 induced by kisspeptin-13 was also observed in pertussis toxin-treated rats, thus suggesting an inhibition independent of G i proteins. In view of the potent insulinostatic effect of kisspeptin-13, it is tempting to speculate that kisspeptins may be implicated in the regulation of B-cell secretion.

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“…In the perfused rat pancreas, 26Rfa has been found to inhibit insulin secretion, but to have no effect on glucagon secretion (Egido et al, 2007). Despite the significant effect of 26Rfa on insulin secretion, however, GPR103 has not been detected in islet cells and thus the signaling mechanism is still unknown.…”

Section: Gpr103mentioning

confidence: 99%

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

Winzell

Åhrén

2007

Pharmacology & Therapeutics

161

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Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G-protein) coupled receptors (GPCRs). Examples of islet GPCRs are GPR40 and GPR119, which are GPCRs with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors

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26RFa, a novel orexigenic neuropeptide, inhibits insulin secretion in the rat pancreas

Cited by 45 publications

References 34 publications

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis

Hypothalamic Neuropeptide 26RFa Acts as an Incretin to Regulate Glucose Homeostasis

Kisspeptin-13 inhibits insulin secretion without affecting glucagon or somatostatin release: study in the perfused rat pancreas

G-protein-coupled receptors and islet function—Implications for treatment of type 2 diabetes

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