Figure 6.

Suppressive effect of SS14, peptide analogs and diazoxide on insulin secretion in islets from healthy donors. Isolated healthy human islets (Prodo Labs, CA) were loaded in a perifusion system (Biorep, FL) and treated over time with 3 mM glucose (G3), 16.7 mM glucose (G16.7), and 16.7 mM glucose + 100 μM tolbutamide (G16.7 + Tolb) in the presence or absence of SS14 and analog peptides, pasireotide, octreotide and lanreotide at 0.1 μM (A and B) and diazoxide at 10 μM and 100 μM (C and D). Insulin secretion was quantified using an ELISA assay (Mercodia, Uppsala, Sweden) and the dynamic stimulation index (dSI) was calculated as stimulated insulin levels/basal insulin levels. (A and C) Mean dSI ± SD (n = 2 technical replicates) from one representative donor. (B and D) Percent insulin secretion was calculated in each condition and compared to the vehicle group which was set to 100%. One-way ANOVA analysis with Dunnett’s multiple comparisons of peptide (B): G16.7 (F(4, 16) = 38.76, p < 0.0001 for all peptide comparisons to vehicle) and G16.7 + Tolb (F(4, 15) = 24.32, p < 0.0001 for all comparisons to vehicle); diazoxide (D): G16.7 (F(2, 12) = 45.27, p = 0.25 for 10 μM, p < 0.0001 for 100 μM compared to vehicle) and G16.7 + Tolb (F(2, 12) = 0.039, p = 0.99 for 10 μM and p = 0.94 for 100 μM compared to vehicle). Data represent mean ± SD from 4 to 6 independent donors in (B) and 3 to 6 independent donors in (D). (Comparison to Vehicle control: ∗∗∗∗, p ≤ 0.0001).