Sigma‑1 receptor (Sig‑1R) is a class of orphan receptors, the potential role of which in pancreatic islet cells remains poorly understood. The present study aimed to investigate the role of Sig‑1R in islet β‑cell proliferation and examine the effects of Sig‑1R on islet β‑cell injury under lipotoxic conditions. Sig‑1R‑overexpressing MIN6 cells were generated by lentiviral vector transfection. The effect of Sig‑1R overexpression on cell proliferation detected by EdU staining, cell cycle progression by
propidium iodide (PI), apoptosis by Annexin V‑APC/PI, mitochondrial membrane potential by Mitolite Red and cytoplasmic Ca2+ levelsby Fura‑2/AM in islet β‑cells were measured by flow cytometry. Western blot analysis was used to measure
protein expression levels of endoplasmic reticulum (ER) stress markers glucose‑regulated
protein 78 and
C/EBP homologous protein, mitochondrial apoptotic
proteins Bcl‑2‑associated X and Bcl‑2 and cytochrome c. In addition,
ATP levels and insulin secretion were separately measured using
ATP Assay and mouse
insulin ELISA. Mitochondria‑associated ER membrane (MAM) structures in MIN6 cells were then detected using transmission electron microscopy.
Protein disulfide isomerase expression and possible colocalization between
inositol 1,4,5‑trisphosphate receptor and voltage‑dependent
anion channel 1 were examined using immunofluorescence. Sig‑1R overexpression was found to promote β‑cell proliferation by accelerating cell cycle progression. Furthermore, Sig‑1R overexpression ameliorated the apoptosis rate whilst impairing insulin secretion induced by
palmitic acid by relieving ER stress and
mitochondrial dysfunction in MIN6 cells. Sig‑1R overexpression also promoted Ca2+ transport between mitochondria and ER by increasing the quantity of ER adjacent to mitochondria in the 50‑nm range. It was concluded that Sig‑1R overexpression conferred protective effects on β‑cells against lipotoxicity as a result of the promotion of cell proliferation and inhibition of ER stress and oxidative stress, by regulating the structure of MAM.