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The glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging

dc.rights.licenseopenen_US
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorABARKAN, Myriam
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGAITAN, Julien
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLEBRETON, Fanny
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorPERRIER, Romain
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorJAFFREDO, Manon
dc.contributor.authorMULLE, Christophe
dc.contributor.authorMAGNAN, Christophe
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorRAOUX, Matthieu
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLANG, Jochen
dc.date.accessioned2020-03-24T09:15:41Z
dc.date.available2020-03-24T09:15:41Z
dc.date.issued2019
dc.identifier.issn2212-8778en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/3935
dc.description.abstractEnOBJECTIVE: Islets secrete neurotransmitters including glutamate which participate in fine regulation of islet function. The excitatory ionotropic glutamate receptor GluK2 of the kainate receptor family is widely expressed in brain and also found in islets, mainly in alpha and gamma cells. alpha cells co-release glucagon and glutamate and the latter increases glucagon release via ionotropic glutamate receptors. However, neither the precise nature of the ionotropic glutamate receptor involved nor its role in glucose homeostasis is known. As isoform specific pharmacology is not available, we investigated this question in constitutive GluK2 knock-out mice (GluK2-/-) using adult and middle-aged animals to also gain insight in a potential role during aging. METHODS: We compared wild-type GluK2+/+ and knock-out GluK2-/- mice using adult (14-20 weeks) and middle-aged animals (40-52 weeks). Glucose (oral OGTT and intraperitoneal IPGTT) and insulin tolerance as well as pyruvate challenge tests were performed according to standard procedures. Parasympathetic activity, which stimulates hormones secretion, was measured by electrophysiology invivo. Isolated islets were used invitro to determine islet beta-cell electrical activity on multi-electrode arrays and dynamic secretion of insulin as well as glucagon was determined by ELISA. RESULTS: Adult GluK2-/- mice exhibit an improved glucose tolerance (OGTT and IPGTT), and this was also apparent in middle-aged mice, whereas the outcome of pyruvate challenge was slightly improved only in middle-aged GluK2-/- mice. Similarly, insulin sensitivity was markedly enhanced in middle-aged GluK2-/- animals. Basal and glucose-induced insulin secretion invivo was slightly lower in GluK2-/- mice, whereas fasting glucagonemia was strongly reduced. Invivo recordings of parasympathetic activity showed an increase in basal activity in GluK2-/- mice which represents most likely an adaptive mechanism to counteract hypoglucagonemia rather than altered neuronal mechanism. Invitro recording demonstrated an improvement of glucose-induced electrical activity of beta-cells in islets obtained from GluK2-/- mice at both ages. Finally, glucose-induced insulin secretion invitro was increased in GluK2-/- islets, whereas glucagon secretion at 2mmol/l of glucose was considerably reduced. CONCLUSIONS: These observations indicate a general role for kainate receptors in glucose homeostasis and specifically suggest a negative effect of GluK2 on glucose homeostasis and preservation of islet function during aging. Our observations raise the possibility that blockade of GluK2 may provide benefits in glucose homeostasis especially during aging.
dc.description.sponsorshipTransistors multimodaux sensibles aux ions à polymères ambivalents pour biocapteurs hybridesen_US
dc.description.sponsorshipIdentification de biomarqueurs du stress et de l'inflammation des cellules B pancréatiques en explorant les communications inter-organes dans des modèles précliniques d'obésité et de diabète de type 2 - ANR-15-CE14-0027en_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subject.enIslets
dc.subject.enKainate receptor
dc.subject.enGRIK2
dc.subject.enGluK2
dc.subject.enAging
dc.subject.enMicroelectrode array
dc.titleThe glutamate receptor GluK2 contributes to the regulation of glucose homeostasis and its deterioration during aging
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.molmet.2019.09.011
dc.subject.halChimie/Matériauxen_US
bordeaux.journalMolecular metabolismen_US
bordeaux.page152-160en_US
bordeaux.volume30en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-02991742
hal.version1
hal.date.transferred2020-11-06T09:20:21Z
hal.exporttrue
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