IGFBP3 and pancreatic insulinoma: Indeed, low expression of TMEM219 was found in insulinoma-derived cells, in which beta cells are prone to proliferate, as well as low levels of the TMEM219 ligand IGFBP3 were detected in the circulation, thereby confirming a dysregulation of the TMEM219 signaling pathway when beta cell homeostasis is perturbed.