Increased expression of ERp57/GRP58 is protective against pancreatic beta cell death caused by autophagic failure

• Expression of ERp57 is increased in Atg7 deleted islets and beta cell lines.
• The suppression of ERp57 enhances apoptotic cell death by autophagic failure in beta cells.
• ERp57 may contribute to the protection from beta cell death by autophagic failure.

Autophagy is a tightly regulated self-digestion system. As in other cell types, autophagy plays an essential role in the homeostasis of pancreatic beta cells. However, the mechanisms involved in the deterioration of beta cell function caused by autophagic failure have not yet been fully elucidated. To gain insight into its mechanisms, we compared the protein expression of islets from beta cell-specific Atg7-deficient mice (Atg7Δβ-cell mice) and their controls (Atg7f/f mice). Liquid chromatography/mass spectrometry after 1-dimensional electrophoresis identified the increased expression of ERp57/GRP58 in islets isolated from Atg7Δβ-cell mice compared with those from Atg7f/f mice. The expression level of ERp57 was also elevated in rat insulinoma INS-1 cells by inducible knock-down of the atg7-gene. In Atg7 knock-down INS-1 cells, the suppression of ERp57 expression by siRNA resulted in an increase in the level of cleaved Caspase-3 protein and a decrease in the number of live cells. Furthermore, cell cycle analyses demonstrated that the suppressed expression of ERp57 increased the sub-G1 population. These data reveal that increased expression of ERp57 may contribute to the protection from beta cell death caused by autophagic failure.