%0 Figure %A Pratt, Evan P. S. %A Harvey, Kyle E. %A Salyer, Amy E. %A Hockerman, Gregory H. %D 2019 %T Effect of PDE inhibitors on GSIS in INS-1 cells and human pancreatic islets. %U https://plos.figshare.com/articles/figure/Effect_of_PDE_inhibitors_on_GSIS_in_INS-1_cells_and_human_pancreatic_islets_/9727187 %R 10.1371/journal.pone.0215188.g004 %2 https://plos.figshare.com/ndownloader/files/17420888 %K PDE 4 activity %K subtype-selective PDE inhibitors %K rat insulinoma cell line INS %K PDE 3 %K PDE 4 inhibitor rolipram %K PDE 4 inhibition %K potentiate glucose-stimulated insulin secretion %K 18 mM glucose %K cAMP levels %K CREB %K potentiated insulin secretion %K PDE 1 %K PDE 3 inhibitor cilostamide %K 1.7 mM glucose %K FRET-based cAMP sensor %K PDE 1 inhibitor 8 MM-IBMX %K PDE 3 inhibition %K PDE 4 inhibition potentiated cAMP levels %K 16.7 mM glucose %K PDE 1 inhibition %X

A) Glucose (18 mM) significantly stimulates insulin secretion above basal levels in INS-1 cells (**, P < 0.01, compared to 0 glucose; Student’s unpaired t-test). Data shown are mean ± SE from four independent experiments. B) Subtype-selective PDE inhibitors and the pan PDE inhibitor IBMX potentiate insulin secretion stimulated with glucose (18 mM) in INS-1 cells. Each experiment was normalized to the glucose response. IBMX (100 μM), 8MM-IBMX (100 μM) and rolipram (10 μM) significantly stimulate insulin secretion, compared with glucose alone. Potentiation of GSIS with cilostamide (1 μM) or rolipram is significantly less than IBMX. Further, insulin secretion stimulated with cilostamide is significantly less than both 8MM-IBMX and rolipram (**, P < 0.01, *, P < 0.05 compared to 18G; #, P < 0.05 compared to IBMX; †, P < 0.05 compared to 8MM-IBMX; ‡, P < 0.05 compared to rolipram; One-way ANOVA, Tukey post-hoc test). Data shown are mean ± SE from four independent experiments. C) Subtype-selective PDE inhibitors and the pan PDE inhibitor IBMX potentiate insulin secretion stimulated with 16.7G in intact human islets isolated from four separate donors. In donor 3, 8MM-IBMX was significantly greater than 1.7G and 16.7G. In donor 4, IBMX was significantly greater than 1.7G and 16.7G, whereas rolipram was significantly less than IBMX. There are no significant differences among the treatment conditions for donor 5. Finally, in donor 6 we observed that IBMX had a significant effect above 1.7G and 16.7G, and 8MM-IBMX was less than IBMX (**, P < 0.01, *, P < 0.05 compared to 1.7G; ##, P < 0.01, #, P < 0.05 compared to 16.7G; †, P < 0.05 compared to IBMX; One-way ANOVA, Tukey post-hoc test). Data shown are mean ± SE from four human islet donors, in which each treatment was performed in triplicate.

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