Figure 3.
d-serine impairs insulin secretion but not islet morphology. (A) 4 week old C57Bl/6 mice were gavaged with 10 mg/kg 13C-labeled d-serine and sacrificed after 60 min. Pancreata were prepared for MALDI FT-ICR MSI and stained with H&E. Control animals were gavaged with water. Size bar represents 2 mm. (B) Quantification of islet size and (C) islet size distribution (n = 4 per group) after 8 weeks of d-serine supplementation. (D) Representative triple staining of pancreatic islets after 3 weeks of serine supplementation. White: somatostatin. Red: glucagon. Green: insulin. Blue: Dapi. Size bar represents 50 μm. (E) Glucose stimulated insulin secretion after 4 weeks of serine supplementation (n = 5). (F) Blood glucose after one week on HFD +/− 10 g/l d-serine and 0.3% dextromethorphan in drinking water following a 4 h fast. (G) Glucose stimulated insulin secretion of isolated pancreatic islets pretreated with either 400 μM d-serine, 10 μM Dextrorphan tartrate (DXO) or a combination thereof for 1 h (n = 4). (H) Representative current-clamp trace of a mouse pancreatic β-cell displaying the electrical response to 400 μM d-serine and 10 μM DXO, in the presence of 2 or 16.7 mM glucose. The graph on the right shows mean membrane potential (n = 3–5). Values are mean ± SEM, analyzed by one-way or two-way ANOVA with Tukey's or Sidaks (for Fig 3E) multiple comparison post-hoc test (****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05).