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Suwandhi, L. ; Hausmann, S. ; Braun, A. ; Gruber, T. ; Heinzmann, S.S. ; Gálvez, E.J.C.* ; Buck, A. ; Legutko, B. ; Israel, A. ; Feuchtinger, A. ; Haythorne, E.* ; Staiger, H. ; Heni, M. ; Häring, H.-U. ; Schmitt-Kopplin, P. ; Walch, A.K. ; Cáceres, C.G.* ; Tschöp, M.H. ; Rutter, G.A.* ; Strowig, T.* ; Elsner, M. ; Ussar, S.

Chronic d-serine supplementation impairs insulin secretion.

Mol. Metab., DOI: 10.1016/j.molmet.2018.07.002 (2018)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Thus, we identify a novel role of d-serine in regulating systemic glucose metabolism through modulating insulin secretion.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Diabetes ; Insulin Secretion ; Obesity ; D-serine
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed