Fig. 2: Loss of electrical coupling in T1D contributes to elevated intraislet somatostatin.
a, Relationship between insulin content and glucagon secretion in isolated islets. The Hill equation (glucagon secretion = 1 ⁄ (1 + (EC50 / (insulin content)h) was fit to the data with an EC50 of 56 ± 9 nmol per islet and an h = 1.9 ± 0.5. b, As in a, but showing the relationship between insulin content and somatostatin secretion. EC50 = 53 ± 6 nmol per islet, h = −2.5 ± 0.5. c, Relationship between somatostatin secretion and glucagon secretion. Line: linear regression fitting of the data (r = 0.669; P < 0.0001). In a–c, data points (n = 60) represent groups of 20 islets (using 12 young ND, 10 adult ND and 10 T1D NOD mice). d,e, Somatostatin (d) and glucagon (e) secretion at 1 mM glucose in islets with or without 24 h CC pretreatment. *P = 0.02, **P = 0.004 vs 1 mM glucose alone (n = 5 using four mice). f, Membrane potential recordings from δ-cells in intact islets treated with saline (left) or CC (right). g, Most negative δ-cell (interspike) potential with or without CC pretreatment. **P = 0.0049 vs control (one-sided unpaired t-test). n = 5 cells in five islets from two mice. h,i, Somatostatin (h) and glucagon secretion (i) at 1 mM glucose with or without MFQ. **P = 0.0095 (in h); **P = 0.0038 (in i) vs 1 mM glucose alone (n = 7 using four mice). j, As in h, but testing the effect of CBX (100 µM). *P = 0.04 vs 1 mM glucose alone (n = 14 using four mice). k,l, Somatostatin (k) and glucagon secretion (l) at 1 mM glucose in islet pretreated or not with CC and in the presence of MFQ or CBX as indicated. **P < 0.01; ***P < 0.001; ****P < 0.0001 vs 1 mM glucose (n = 6 using four mice). m,n, Somatostatin (m) and glucagon (n) secretion at 1 mM glucose in islets from T1D NOD mice with or without MFQ as indicated (n = 5 using five T1D NOD mice; blood glucose >33 mM). Somatostatin secretion at 1 mM glucose alone was higher than in young ND NOD mice (P = 0.0115). Two-sided unpaired t-test was used in d, e and h–n. In dot plots, rectangles and error bars behind data points represent mean values ± s.e.m. CC, cytokine cocktail.
