Endoplasmic reticulum stress induced by lipopolysaccharide is involved in the association between inflammation and autophagy in INS-1 cells

Type 2 diabetes is a chronic inflammatory disease. Autophagy, the dynamic process of lysosomal degradation of damaged organelles and proteins, may protect β-cells from destruction by inflammation in type 2 diabetes. The present study investigated the role of autophagy, inflammation and endoplasmic reticulum (ER) stress in type 2 diabetes. INS-1 cells were incubated with lipopolysaccharide. The chemical chaperone 4-phenylbutyric acid was used to inhibit ER stress, and 3-methyadenine (3-MA) was used to inhibit autophagy. Apoptosis was detected by flow cytometry and cell proliferation using Cell Counting kit-8 solution. Light chain-3B, interleukin (IL) 1β, caspase-1 and C/EBP homologous protein production were assessed by western blotting, and rat activating transcription factor 4 and rat binding immunoglobulin heavy chain protein gene expression were determined by real-time reverse transcription-polymerase chain reaction. The results showed that inhibiting autophagy with 3-MA unexpectedly contributed to cell death in β-cells. This response was associated with an increase in inflammatory cytokines, including IL1β and caspase-1. Inhibiting ER stress with 4-phenylbutyric acid led to a decrease in cell apoptosis. These results showed that autophagy may have a protective effect by reducing inflammatory cytokines in β-cells. In addition, the inositol-requiring enzyme 1 pathway mediated the ER stress associated with autophagy and inflammatory cytokines (IL1β and caspase-1). Therefore, inflammatory cytokines may be critical signalling nodes, which are associated with ER stress-mediated β-cell death.