Fig. 3: β-cell hyperpolarization via gap junctions prevents δ-cell electrical activity and somatostatin secretion.
a,b, Examples of light-induced currents (a) and changes in membrane potential (b) in δ-cells of RIP-NpHR islets exposed to 10 mM glucose. Horizontal bars above the traces indicate onset of light activation (625 nm). In a, red dashed line indicates baseline. c, Amplitudes of light-induced currents (ΔI) in δ-cells ±200 μM CBX. Insets show δ-cell current excursions during optoactivation of NpHR in β-cells at 1 mM glucose in the absence (Ctrl) and presence of CBX. *P = 0.0328 vs no CBX (n = 7 cells without and n = 8 cells with CBX from seven mice). d, As in c but membrane potential changes (ΔVm) were measured. ****P = 1.4 × 10−6 (n = 17 cells without and n = 8 cells with CBX from seven mice). e, Somatostatin secretion in RIP-NpHR islets at 1 mM and 20 mM glucose ±NpHR activation in β-cells. ***P = 0.0009, ****P = 3.3 × 10−5 vs 1 mM glucose alone (±light activation); †P = 0.0126 vs 20 mM glucose without light activation (n = 11–16 experiments using islets from six mice). f, Membrane resistance in δ-cells at 1 mM glucose in islets from control and β-V59M mice. P = 0.96 vs control islets (n = 13 cells from eight control mice and n = 5 cells from four β-V59M mice). g, Electrical activity recorded from a δ-cell in a control islet at indicated glucose concentrations. Representative of five δ-cells from five mice. h, As in g but experiment performed in a δ-cell in an islet from hyperglycaemic β-V59M mouse 48 h after induction of the transgene expression (and diabetes) with tamoxifen. Representative of three δ-cells from three mice. i, Effects of injection of negative current (−1, −2 and −4 pA; top) on electrical activity (lower) in δ-cells at 10 mM glucose. j, Minimal current required to inhibit δ-cell electrical activity (n = 7 cells from five mice). Two-sided unpaired t-test was used in c–f. In dot plots, rectangles and error bars behind data points represent mean values ± s.e.m. WT, wild type.
