Figure 4. Accelerated glucose metabolism promotes insulin hypersecretion in Lsd1^Δβ islets.

(A) Oxygen consumption rate (OCR) of islets treated sequentially with the indicated glucose concentrations (in mM), oligomycin (OM), and antimycin A (AM). n = 8–10 pools of 60 islets. ***P < 0.001, 2-way ANOVA for genotype for each time block. (B) ATP content of islets. n = 9–10 pools of 20 islets. *P < 0.05, unpaired 2-tailed t test. (C and D) Intracellular Ca²⁺ concentration of β cells treated with glucose (in mM) (C) or the K_ATP channel opener diazoxide (Dz) (D). n = 32–46 β cells, representative of 3 independent experiments. ***P < 0.001, 2-way ANOVA for genotype for each time block. ^#P < 0.05; ^###P < 0.001, 2-way ANOVA for the interaction between genotype and time for each time block. (E) Insulin-secretion by islets with and without Dz. n = 5–6 pools of 10 islets. **P < 0.01; ***P < 0.001, pairwise t test corrected for multiple comparisons with the Benjamini-Hochberg procedure following 2-way ANOVA for genotype and stimulation condition. (F) Schematic of tracing experiment. (G and H) Molar percentage enrichment (MPE) of ¹³C (G) and relative abundances (H) of indicated metabolites after tracing with 2.8 mM U-¹³C glucose. n = 3 pools of 220 islets. ***P < 0.001, unpaired 2-tailed t test. (I and J) Insulin secretion by islets under depolarizing conditions (30 mM KCl and 100 μM Dz) (I) or with and without the glycolysis inhibitor mannoheptulose (Mh) (J). n = 5–6 pools of 10 islets. *P < 0.05; **P < 0.01; ***P < 0.001, pairwise t test corrected for multiple comparisons with the Benjamini-Hochberg procedure following 2-way ANOVA for genotype and stimulation condition. Islets were isolated from ad libitum–fed animals 3 weeks following tamoxifen treatment. Data are represented as mean ± SEM.