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dc.contributor.authorSuwandhi, Lisa
dc.contributor.authorHausmann, Simone
dc.contributor.authorBraun, Alexander
dc.contributor.authorGruber, Tim
dc.contributor.authorHeinzmann, Silke S
dc.contributor.authorGálvez, Eric J C
dc.contributor.authorBuck, Achim
dc.contributor.authorLegutko, Beata
dc.contributor.authorIsrael, Andreas
dc.contributor.authorFeuchtinger, Annette
dc.contributor.authorHaythorne, Elizabeth
dc.contributor.authorStaiger, Harald
dc.contributor.authorHeni, Martin
dc.contributor.authorHäring, Hans-Ulrich
dc.contributor.authorSchmitt-Kopplin, Philippe
dc.contributor.authorWalch, Axel
dc.contributor.authorCáceres, Cristina García
dc.contributor.authorTschöp, Matthias H
dc.contributor.authorRutter, Guy A
dc.contributor.authorStrowig, Till
dc.contributor.authorElsner, Martin
dc.contributor.authorUssar, Siegfried
dc.date.accessioned2018-08-29T07:44:58Z
dc.date.available2018-08-29T07:44:58Z
dc.date.issued2018-07-25
dc.identifier.issn2212-8778
dc.identifier.pmid30093356
dc.identifier.doi10.1016/j.molmet.2018.07.002
dc.identifier.urihttp://hdl.handle.net/10033/621458
dc.description.abstractThe metabolic role of d-serine, a non-proteinogenic NMDA receptor co-agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA receptors as well as loss of the d-serine producing enzyme serine racemase have been shown to modulate insulin secretion. Thus, we aim to study the impact of chronic and acute d-serine supplementation on insulin secretion and other parameters of glucose homeostasis. We apply MALDI FT-ICR mass spectrometry imaging, NMR based metabolomics, 16s rRNA gene sequencing of gut microbiota in combination with a detailed physiological characterization to unravel the metabolic action of d-serine in mice acutely and chronically treated with 1% d-serine in drinking water in combination with either chow or high fat diet feeding. Moreover, we identify SNPs in SRR, the enzyme converting L-to d-serine and two subunits of the NMDA receptor to associate with insulin secretion in humans, based on the analysis of 2760 non-diabetic Caucasian individuals. We show that chronic elevation of d-serine results in reduced high fat diet intake. In addition, d-serine leads to diet-independent hyperglycemia due to blunted insulin secretion from pancreatic beta cells. Inhibition of alpha 2-adrenergic receptors rapidly restores glycemia and glucose tolerance in d-serine supplemented mice. Moreover, we show that single nucleotide polymorphisms (SNPs) in SRR as well as in individual NMDAR subunits are associated with insulin secretion in humans. Thus, we identify a novel role of d-serine in regulating systemic glucose metabolism through modulating insulin secretion.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectDiabetesen_US
dc.subjectInsulin secretionen_US
dc.subjectObesityen_US
dc.subjectd-serineen_US
dc.titleChronic d-serine supplementation impairs insulin secretion.en_US
dc.typeArticleen_US
dc.contributor.departmentHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en_US
refterms.dateFOA2018-08-29T07:44:59Z
dc.source.journaltitleMolecular metabolism


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