In INS-1E rat insulinoma cells, Skrzypski et al. (2016) showed that orexin-A at 100 nM activates extracellular signal-regulated kinase 1/2 (ERK1/2) to drive cell cycle progression and proliferation, while independently engaging transient receptor potential (TRP) channels to elevate intracellular calcium and trigger insulin secretion effects that were unaffected by changes in insulin mRNA, indicating post-transcriptional regulation. The gene discussed is INS; the disease is pancreatic insulinoma.