| A major obstacle to islet transplantation is beta-cell death following isolation. Isolation exposes islets to various stresses including endoplasmic reticulum (ER) stress inducers; therefore, the role of ER stress signaling in isolated islet apoptosis was investigated. Activation of eIF2alpha and JNK1 and XBP1 splicing followed by an increase in caspase-3 activity were observed in isolated human islets. Since the absence of protein-tyrosine phosphatase 1B (PTP1B) was previously shown to reduce ER stress-induced signaling and apoptosis in fibroblasts, the role of PTP1B in ER stress signaling was investigated in beta-cells. While encouraging data emerged, using an inhibitor and miRNA targeting PTP1B, a conclusive link between PTP1B inhibition and improved beta-cell survival has not yet been seen. This study provides the first evidence that ER stress signaling may influence isolated islet apoptosis and could point to novel therapeutic approaches in islet transplantation. |
