Acute D-Serine Co-Agonism of β-Cell NMDA Receptors Potentiates Glucose-Stimulated Insulin Secretion and Excitatory β-Cell Membrane Activity.

ABSTRACT: Insulin-secreting pancreatic β-cells express proteins characteristic of D-serine regulated synapses, but the acute effect of D-serine co-agonism on its presumptive β-cell target, N-methyl D-aspartate receptors (NMDARs), is unclear. We used multiple models to evaluate glucose homeostasis and insulin secretion in mice with a systemic increase in D-serine (intraperitoneal injection or DAAO mutants without D-serine catabolism) or tissue-specific loss of Grin1-encoded GluN1, the D-serine binding NMDAR subunit. We also investigated the effects of D-serine ± NMDA on glucose-stimulated insulin secretion (GSIS) and β-cell depolarizing membrane oscillations, using perforated patch electrophysiology, in β-cell-containing primary isolated mouse islets. In vivo models of elevated D-serine correlated to

SUBMITTER: Lockridge A 

PROVIDER: S-EPMC7826616 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature