Fig. 1.

Glucose stimulation increases IP₇ levels via IP6K1. (A) IP₇/IP₆ ratios obtained at various time points following 10 mM glucose stimulation of MIN6m9 cells (n = 3–4). There is a significant increase in IP₇/IP₆ levels between zero and 3 min of glucose stimulation, **p < 0.01, one-way ANOVA followed by Tukey's multiple comparison. (B) The comparison between stimulation with 0.5 and 10 mM glucose for 3 min showed a 34% increase in IP₇ levels in MIN6m9 cells (n = 3). (C, D) Exposure to 16.7 mM glucose for 3 min induced an IP₇ response in C57BL/6 mouse islets, n = 4 preparations, and human islets, n = 3 donors, *p < 0.05, 95% confidence interval, in panels B-D. (E) ATP/ADP ratios obtained at various time points following 10 mM glucose stimulation of MIN6m9 cells (n = 3–4). There is a significant increase in ATP/ADP levels between zero and 3 min of glucose stimulation, *p < 0.05, one-way ANOVA followed by Tukey's multiple comparison. IP₇ is produced by other metabolic fuels that increase ATP/ADP ratio. When MIN6m9 cells were stimulated with either 10 mM pyruvate or 10 mM leucine for 3 min, there was a significant increase in both ATP/ADP ratio, n = 3, (F) and IP₇/IP₆ levels, n = 4, (G), **p < 0.01, *p < 0.05, one-way ANOVA followed by Tukey's multiple comparison. (H) In MIN6m9 cells, silencing IP6K1 blocked the increase of IP₇ induced by 10 mM glucose stimulation for 3 min, n = 3, *p < 0.05, two-way ANOVA (Supplemental Table S1). All bars and plots are means ± SEM.