Fig. 4: Effects of T1D on glucagon and somatostatin secretion in human islets.
a–c, Glucagon secretion in human islets from ND donors at 6 mM and 1 mM glucose (6G and 1G) (n = 50, ten donors) (a), at 1 mM glucose ±100 nM CYN154806 (n = 41, eight donors) (b) or 6 mM amino acids (AA) (n = 27, four donors) (c). ****P = 6.676 × 10−10 (glucose) and ****P = 3.446*10−5 (AA). ****P = 7.7 × 10−5 (inset in a) and *P = 0.0362 (inset in c). d, Glucagon secretion in islets from donors with T1D at 6 mM and 1 mM glucose (n = 31–36 experiments, six donors) or ±CYN154806 or amino acids as indicated (n = 20 experiments, four donors). *P = 0.015, ***P = 0.00015, ****P < 0.0001. e, Somatostatin secretion at 1 mM glucose in islets from ND donors (n = 56, nine donors) and donors with T1D (n = 31, four donors). ****P = 1.8 × 10−5, **P = 0.004 (inset). f,g, Somatostatin (f) and glucagon (g) secretion at 1 mM glucose in islets from ND donors ±CC pretreatment for 24 h (n = 25, five donors). **P = 0.00105 (somatostatin), ***P = 0.00049 (glucagon) vs no CC. In insets, **P = 0.0024 (glucagon), **P = 0.0045 (somatostatin). h,i, Somatostatin (h) and glucagon (i) secretion at 1 mM glucose in islets from ND donors with or without MFQ (n = 21, four donors for somatostatin and n = 17, three donors for glucagon). ***P = 0.0005 (somatostatin), ****P = 9.39 × 10−5 (glucagon) vs control. In insets, *P = 0.035 (somatostatin) and **P = 0.002 (glucagon). j, Mathematical modelling of the fraction of δ-cells in contact with at least one β-cell expressed as a function of fraction β-cells deleted (%) in individual islets and mean of six islets. Shaded area, 95% confidence interval. Dotted lines, >90% of δ-cells are in contact with at least one β-cell until ~75% of β-cells have been removed. Rectangles and error bars behind data points represent mean values ± s.e.m. In a–i, different colours are used for each donor. Insets show mean data of the individual donors. Two-tailed unpaired t-test was used in a–c and e–i, one-way ANOVA with Tukey’s post hoc test was used in d and one-tailed paired t-test was used in the insets in a–d and f–i. One-tailed unpaired t-test was used in the inset of e.
