Fig. 3.

Dependence of encapsulated islet functionality on oxygen conditions. (A and B) In vitro low (A, 2 mM) and high (B, 20 mM) glucose-stimulated insulin secretion assay (GSIS) of encapsulated islets (500 islet equivalents per group) under different oxygen conditions (21%, shaded bars; 10%, cross-hatched bars; 8%, solid bars; 3%, shaded hatched diagonal bars). From the high-glucose GSIS assay it is evident that at 3% pO₂ (shaded hatched diagonal bars) the amount of secreted insulin is below the threshold of 8 ng/mL (red dashed line) necessary for curing diabetes in adult mice when implanted with 500 islet equivalents. At 8–10% pO₂ (solid and cross-hatched bars), which is within the average range of oxygen pressure in the IP space of mice, the amount of secreted insulin is borderline above the therapeutic threshold. Measurements were performed daily over a period of 4 d. (C and D) High-glucose GSIS data over a 12-d period where the pO₂ is changed every 4 d (C) and is maintained at 21% for the full 12-d period (D). Even under normoxic conditions (D) islet functionality deteriorates over time. For all graphs values are mean ± SEM. All experiments were repeated at least twice. Groups were compared with a nonparametric, pairwise Wilcox test with Benjamini and Hochberg (BH) correction for multiple comparisons (*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns, not significant).