The neuropeptide 26RFa in the human gut and pancreas: potential involvement in glucose homeostasis

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Les déterminants environnementaux et génétiques de phénotypes intermédiaires de l'inflammation dans la cohorte STANISLAS

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocSudocFranceF

Variations pré-analytiques des biomarqueursprotéiques

Dans le domaine des protéines, le résultat d’une analyse a pendant longtemps été dépendant de variations des conditions analytiques. Actuellement, du fait de l’évolution des technologies et des contrôles, ces variations sont beau-coup plus faibles que celles dues aux conditions pré-analytiques, très difficiles à maîtriser. Les raisons en sont qu’elles sont nombreuses et pas toujours connues du biologiste. Nous présentons dans cet article les principaux facteurs de variation pré-analytique, ainsi que leurs effets sur les résultats des analyses. Les résultats obtenus grâce aux nouvelles techniques de détermination par spectrométrie de masse sont très prometteurs, mais très sensibles à des paramètres tels que la stabilité des échantillons et le type d’anticoagulant utilisé. Il est donc de plus en plus nécessaire de prendre en compte ces données souvent ignorées

Le neuropeptide 26RFa : un nouveau régulateur de l’homéostasie énergétique

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The Neuropeptide 26RFa (QRFP) and Its Role in the Regulation of Energy Homeostasis: A Mini-Review

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Interactions between the regulatory peptide 26RFa (QRFP) and insulin in the regulation of glucose homeostasis in two complementary models: The high fat 26RFa-deficient mice and the streptozotocin insulin-deficient mice

International audienceThe regulatory peptide 26RFa (QRFP) is involved in the control of glucose homeostasis at the periphery by acting as an incretin, and in the brain by mediating the central antihyperglycemic effect of insulin, indicating the occurrence of a close relationship between 26RFa and insulin in the regulation of glucose metabolism. Here, we investigated the physiological interactions between 26RFa and insulin in two complementary models i.e. a model of obese/hyperglycemic mice deficient for 26RFa and a model of diabetic mice deficient for insulin. For this, transgenic 26RFa-deficient mice were made obese and chronically hyperglycemic by a 3-month high fat diet (HFD) and second group of mice was made diabetic by destruction of the β cells of the pancreatic islets using a single injection of streptozotocin. Our data reveal that 26RFa deficiency does not impact significantly the “glycemic” phenotype of the HFD mice. The pancreatic islets, liver, white adipose tissue masses are not altered by the lack of 26RFa production but the brown adipose tissue (BAT) weight is significantly increased in these animals. In diabetic insulin-deficient mice, the injection of 26RFa does not exhibit any beneficial effect on the impaired glucose homeostasis characterizing this model. Finally, we show that streptozotocin diabetic mice display lowered plasma 26RFa levels as compared to untreated mice, whereas the expression of the peptide in the duodenum is not affected. Taken together, the present results indicate that dysregulation of glucose homeostasis in obese/hyperglycemic mice is not aggravated by the absence of 26RFa that may be compensated by the increase of BAT mass. In diabetic insulin-deficient mice, the antihypergycemic effect of 26RFa is totally blunted probably as a result of the impaired insulin production characterizing this model, avoiding therefore the action of the peptide

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

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Acute but not chronic central administration of the neuropeptide 26RFa (QRFP) improves glucose homeostasis in obese/diabetic mice

International audienceIntroduction: The aim of the study is to investigate whether acute or chronic central administration of the hypothalamic neuropeptide 26RFa may ameliorate the glycemic control of obese/diabetic mice. Methods: mice were treated for 4 months with a high fat diet (HF) and received a single i.c.v. injection of 26RFa (3 µg) or a chronic i.c.v. administration of the peptide during 28 days via osmotic minipumps (25 µg/day). i.p. and oral glucose tolerance tests, insulin tolerance test, glucose-stimulated insulin secretion, food/water intake, horizontal/vertical activity, energy expenditure, meal pattern and whole body composition were monitored. In addition, 26RFa and GPR103 mRNA expression as well as plasma 26RFa levels were evaluated by RT-QPCR and radioimmunoassay. Results: Acute administration of 26RFa in HF mice induced a robust anti-hyperglycemic effect by enhancing insulin secretion whereas chronic administration of the neuropeptide is unable to improve glucose homeostasis in these obese/diabetogenic conditions. By contrast, chronic 26RFa treatment induced an increase of the body weight accompanied with an enhanced food intake and a decreased energy expenditure. Finally, we show that the HF diet does not alter the hypothalamic expression of the 26RFa/GPR103 neuropeptidergic system nor the levels of circulating 26RFa. Conclusion: Our data indicate that the central beneficial effect of 26RFa on glucose homeostasis, by potentiating glucose-stimulated insulin secretion, is preserved in HF mice. However, chronic administration of the neuropeptide is unable to balance glycemia in these pathophysiological conditions, suggesting that the hypothalamic 26RFa/GPR103 neuropeptidergic system mainly affects short term regulation of glucose metabolism

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

International audienceRecent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. Using a mouse model of high-fat diet-induced obesity and hyperglycemia, we found a loss of the anti-hyperglcemic effect and insulinotropic activity of 26RFa, accompanied with a marked reduction of its insulin-sensitive effect. Interestingly, this resistance to 26RFa is associated with a down-regulation of the 26RFa receptor in the pancreatic islets, and insulin target tissues. Finally, we observed that the production and release kinetics of 26RFa after an oral glucose challenge is profoundly altered in the high-fat mice. Altogether, the present findings support the view that 26RFa is a key regulator of glucose homeostasis whose activity is markedly altered under obese/hyperglycemic conditions