Pathological β-Cell Endoplasmic Reticulum Stress in Type 2 Diabetes: Current Evidence

The notion that in diabetes pancreatic beta-cells express endoplasmic reticulum (ER) stress markers indicative of increased unfolded protein response (UPR) signaling is no longer in doubt. However, what remains controversial is whether this increase in ER stress response actually contributes importantly to the beta-cell failure of type 2 diabetes (akin to 'terminal UPR'), or whether it represents a coping mechanism that represents the best attempt of beta-cells to adapt to changes in metabolic demands as presented by disease progression. Here an intercontinental group of experts review evidence for the role of ER stress in monogenic and type 2 diabetes in an attempt to reconcile these disparate views. Current evidence implies that pancreatic beta-cells require a regulated UPR for their development, function and survival, as well as to maintain cellular homeostasis in response to protein misfolding stress. Prolonged ER stress signaling, however, can be detrimental to beta-cells, highlighting the importance of optimal UPR for ER homeostasis, beta-cell function and survival.

Automated summary

The expression of endoplasmic reticulum (ER) stress markers in pancreatic beta-cells in response to diabetes is confirmed, but the debate lies in whether this stress response contributes to beta-cell failure in type 2 diabetes. Current evidence suggests that regulated unfolded protein response (UPR) is essential for beta-cell development, function, and survival, while prolonged ER stress signaling can be detrimental to beta-cells.