Linking insulin secretion to endoplasmic reticulum stress

A link between endoplasmic reticulum (ER) stress signalling and insulin production and secretion is reported this week in Nature Cell Biology. These findings could open new opportunities for the development of treatments for diabetes.

Mutations in the gene Wolfram syndrome 1 (WFS1) cause Wolfram syndrome, which is characterized by juvenile diabetes. WFS1 is known to regulate ER stress signalling - which disrupts the normal ER protein folding function - and is essential for the normal function of insulin-producing pancreatic beta cells.

Sonya Fonseca and colleagues report that WFS1 has a further role in regulating insulin release from pancreatic beta cells in mice. Glucose - which accumulates in the bloodstream after a meal - causes WFS1 to move to the plasma membrane to simulate insulin production and secretion. The authors also showed that expressing high levels of WFS1 restored insulin secretion in pancreatic beta cells suffering from ER stress. They conclude that WFS1 could therefore represent an important target for new diabetes treatments.