Figure 1.

JB253 bulk synthesis. (a) An alternative synthetic route affords JB253 via crystallization and no chromatography from 1 equivalent of base in the second step. This can be easily performed on the gram-scale, is more environmentally-friendly and allows significant cost reductions and enhanced yield. (b) trans-JB253 (dark) is inactive, whereas illumination with blue light leads to cis-isomerization and activation. (c) Schematic showing that exogenously-applied JB253 closes K_ATP channels, leading to membrane depolarization, Ca²⁺ influx and insulin release. This process can be switched back and forth using light of the appropriate wavelength, or the dark (hv₁ = photon energy needed for isomerization to achieve channel closure; hv₂ = photon energy needed for isomerization to achieve channel opening, also achievable by thermal relaxation k _B T) (see also ref. 10). (d) Representative traces showing that JB253 produced using bulk synthesis allows the reversible optical control of Ca²⁺ fluxes in vitro in isolated pancreatic islets incubated with 8 mm D-glucose. (e) As for (d), but summary bar graph showing Ca²⁺ levels before, during and after illumination with blue light (representative traces; n = 9 recordings from 3 animals). **P < 0.01; repeated measures one-way ANOVA (Bonferroni’s posthoc test). Values represent mean + SEM.