Fig. 1.

Inhibition of GPR44 results in reduced apoptosis and improved function in human islets. (a) Caspase 3/7 activity in human islets treated with 15(R)-15-methyl-PGD₂ (1, 10 and 100 nmol/l) with or without AZ8154 (10 μmol/l) for 24 h, n = 3, with each incubation condition run in duplicate. (b) Caspase 3/7 activity in human islets treated with a proinflammatory cytokine mix (10 ng/ml IL-1β, 50 ng/ml TNF-α and 50 ng/ml INF-γ) with or without AZ8154 (1, 3 and 10 μmol/l) for 24 h, n = 3–9, with each incubation condition run in duplicate. (c) Apoptosis evaluated in isolated human islets treated with either AZ8154 (10 μmol/l) or HG (20 mmol/l) + IL-1β (10 ng/ml) with or without AZ8154 (10 μmol/l) for 48 h, n = 7 individual donors. (d, e) Insulin secretion in response to basal (1.67 mmol/l) and stimulated (20 mmol/l) levels of glucose measured by EIA (d) and calculated as stimulation index (e) for human islets treated with either AZ8154 (10 μmol/l) or HG (20 mmol/l) + IL-1β (10 ng/ml) with or without AZ8154 (10 μmol/l) for 48 h, n = 6 independent donors. In all analyses, data are presented as means ± SD and analysed by one-way ANOVA with Bonferroni corrections. *p < 0.05, **p < 0.01 and ***p < 0.001; Abs., absorbance; PCM, proinflammatory cytokine mix (IL1-β, TNF-α and INF-γ); RLU, relative light units