Persistent ER stress in pancreatic β-cells contributes to the pathogenesis of type 2 diabetes. Fonseca and colleagues show that the ER membrane glycoprotein WFS1, which is mutated in people with Wolfram syndrome, has a known role in the ER stress response. It regulates insulin production and secretion in β-cells by associating with adenylyl cyclase 8 at the plasma membrane and generating cAMP. ER stress prevents WFS1 plasma membrane localization, attenuating cAMP production and insulin secretion.
- Sonya G. Fonseca
- Fumihiko Urano
- Mark Burcin
