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Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
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Chronic d-serine supplementation impairs insulin secretion
Lisa Suwandhi1, Simone Hausmann1, Alexander Braun2
1RG Adipocytes & Metabolism, Institute for Diabetes & Obesity, Helmholtz Center Munich, 85748 Garching, Germany; German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
Molecular Metabolism
|August 11, 2018
Summary
d-serine supplementation impairs insulin secretion, leading to hyperglycemia. Alpha 2-adrenergic receptor inhibition can restore glucose homeostasis, revealing d-serine
Area of Science:
- Metabolic research
- Neuroscience
- Endocrinology
Background:
- The metabolic functions of d-serine, an NMDA receptor co-agonist, are not well understood.
- Pancreatic NMDA receptor activity and serine racemase influence insulin secretion.
Purpose of the Study:
- To investigate the effects of chronic and acute d-serine supplementation on insulin secretion and glucose homeostasis.
- To explore the role of d-serine in regulating systemic glucose metabolism.
Main Methods:
- Utilized MALDI FT-ICR mass spectrometry imaging, NMR metabolomics, and 16s rRNA gene sequencing in mice.
- Administered d-serine in drinking water with chow or high-fat diets.
- Analyzed human genetic data (2760 individuals) for SNPs in SRR and NMDA receptor subunits.
Main Results:
- Chronic d-serine elevated blood glucose (hyperglycemia) by reducing insulin secretion, independent of diet.
- Reduced high-fat diet intake was observed with chronic d-serine.
- Alpha 2-adrenergic receptor inhibition rapidly normalized glycemia and glucose tolerance.
- Human SNPs in SRR and NMDAR subunits correlated with insulin secretion.
Conclusions:
- d-serine plays a significant role in regulating systemic glucose metabolism.
- d-serine modulates insulin secretion from pancreatic beta cells.
- Targeting alpha 2-adrenergic receptors may offer therapeutic potential for d-serine-induced metabolic disturbances.
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