Chronic d-serine supplementation impairs insulin secretion.
dc.contributor.author | Suwandhi, Lisa | |
dc.contributor.author | Hausmann, Simone | |
dc.contributor.author | Braun, Alexander | |
dc.contributor.author | Gruber, Tim | |
dc.contributor.author | Heinzmann, Silke S | |
dc.contributor.author | Gálvez, Eric J C | |
dc.contributor.author | Buck, Achim | |
dc.contributor.author | Legutko, Beata | |
dc.contributor.author | Israel, Andreas | |
dc.contributor.author | Feuchtinger, Annette | |
dc.contributor.author | Haythorne, Elizabeth | |
dc.contributor.author | Staiger, Harald | |
dc.contributor.author | Heni, Martin | |
dc.contributor.author | Häring, Hans-Ulrich | |
dc.contributor.author | Schmitt-Kopplin, Philippe | |
dc.contributor.author | Walch, Axel | |
dc.contributor.author | Cáceres, Cristina García | |
dc.contributor.author | Tschöp, Matthias H | |
dc.contributor.author | Rutter, Guy A | |
dc.contributor.author | Strowig, Till | |
dc.contributor.author | Elsner, Martin | |
dc.contributor.author | Ussar, Siegfried | |
dc.date.accessioned | 2018-08-29T07:44:58Z | |
dc.date.available | 2018-08-29T07:44:58Z | |
dc.date.issued | 2018-07-25 | |
dc.identifier.issn | 2212-8778 | |
dc.identifier.pmid | 30093356 | |
dc.identifier.doi | 10.1016/j.molmet.2018.07.002 | |
dc.identifier.uri | http://hdl.handle.net/10033/621458 | |
dc.description.abstract | The 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.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
dc.subject | Diabetes | en_US |
dc.subject | Insulin secretion | en_US |
dc.subject | Obesity | en_US |
dc.subject | d-serine | en_US |
dc.title | Chronic d-serine supplementation impairs insulin secretion. | en_US |
dc.type | Article | en_US |
dc.contributor.department | Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. | en_US |
refterms.dateFOA | 2018-08-29T07:44:59Z | |
dc.source.journaltitle | Molecular metabolism |