BibTex format
@article{Suwandhi:2018:10.1016/j.molmet.2018.07.002,
author = {Suwandhi, L and Hausmann, S and Braun, A and Gruber, T and Heinzmann, SS and Gálvez, EJC and Buck, A and Legutko, B and Israel, A and Feuchtinger, A and Haythorne, E and Staiger, H and Heni, M and Häring, H-U and Schmitt-Kopplin, P and Walch, A and Cáceres, CG and Tschöp, MH and Rutter, GA and Strowig, T and Elsner, M and Ussar, S},
doi = {10.1016/j.molmet.2018.07.002},
journal = {Molecular Metabolism},
pages = {191--202},
title = {Chronic d-serine supplementation impairs insulin secretion},
url = {http://dx.doi.org/10.1016/j.molmet.2018.07.002},
volume = {16},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Suwandhi,L
AU - Hausmann,S
AU - Braun,A
AU - Gruber,T
AU - Heinzmann,SS
AU - Gálvez,EJC
AU - Buck,A
AU - Legutko,B
AU - Israel,A
AU - Feuchtinger,A
AU - Haythorne,E
AU - Staiger,H
AU - Heni,M
AU - Häring,H-U
AU - Schmitt-Kopplin,P
AU - Walch,A
AU - Cáceres,CG
AU - Tschöp,MH
AU - Rutter,GA
AU - Strowig,T
AU - Elsner,M
AU - Ussar,S
DO - 10.1016/j.molmet.2018.07.002
EP - 202
PY - 2018///
SN - 2212-8778
SP - 191
TI - Chronic d-serine supplementation impairs insulin secretion
T2 - Molecular Metabolism
UR - http://dx.doi.org/10.1016/j.molmet.2018.07.002
UR - https://www.ncbi.nlm.nih.gov/pubmed/30093356
UR - http://hdl.handle.net/10044/1/62319
VL - 16
ER -