Figure 3. Lsd1 inactivation in β cells causes insulin hypersecretion and hypoglycemia.

(A) Schematic of alleles and treatments used to inactivate Lsd1. TM, tamoxifen; q2d, every other day. (B) Immunofluorescence staining for insulin (Ins) and Lsd1 on pancreas sections from control (control TM-treated Lsd1^fl/+; Pdx1-CreER) and Lsd1^Δβ mice 2 days after TM treatment. Scale bars: 50 μm. (C) Time course of ad libitum–fed blood glucose levels in control (TM-treated Lsd1^+/+; Pdx1-CreER) and Lsd1^Δβ mice. n = 9–10 mice. Pre-TM, within 3 days prior to initial TM injection. ***P < 0.001, unpaired 2-tailed t test. (D and E) Blood glucose (D) and serum insulin (E) levels in ad libitum–fed and 16 hour–fasted mice. n = 5–15 mice. *P < 0.05; **P < 0.01; ***P < 0.001, unpaired, 2-tailed t test. (F and G) Insulin secretion by control and Lsd1^Δβ islets during perifusion with the indicated glucose (Glc) concentrations (in mM) at 1 week (F) and 3 weeks (G) following TM treatment. n = 4 pools of 130 islets. Right (F), data shown at a reduced scale. *P < 0.05; ***P < 0.001, 2-way ANOVA for genotype for each time block. (H) Insulin secretion by control and Lsd1^Δβ islets during perifusion with the indicated glucose concentrations (in mM) from mice that were feeding entrained and then fed or fasted as in Supplemental Figure 1A. n = 3 pools of 130 islets. Right, data shown at a reduced scale for the indicated time points. **P < 0.01; ***P < 0.001, 2-way ANOVA for genotype between fed islets for each time block. ^#P < 0.05; ^###P < 0.001, 2-way ANOVA for genotype between fasted islets for each time block. Data are represented as mean ± SEM.