Silenced CHOP protects pancreatic B‐cell function by targeting peroxisome proliferator‐activated receptor‐γ coactivator‐1α through nuclear factor‐κB signaling pathway in diabetes mellitus

摘要

Abstract Aims Diabetes mellitus (DM) is one of the most common metabolic diseases worldwide characterized by insulin resistance and pancreatic β‐cell dysfunction. In the previous study, endoplasmic reticulum (ER) stress could increase the C/EBP homologous protein (CHOP) expression through inhibiting C/EBβ transcriptional activity. However, the role of CHOP and peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) in pancreatic β‐cell dysfunction remains unknown. The aim of the study was to investigate the effect of CHOP and PGC‐1α in pancreatic β‐cell dysfunction and the potential mechanisms underlying its actions. Methods We established the pancreatic β‐cell dysfunction model to identify the biological features and functions of CHOP. Apoptosis was detected using Western blot analysis and real‐time polymerase chain reaction (RT‐PCR). Results Our results showed that high glucose (HG) increases CHOP and inhibits PGC‐1α expression and ameliorates apoptosis in pancreatic β cells. Silenced CHOP elevates the PGC‐1α expression and ameliorates HG‐induced apoptosis in pancreatic β cells. Furthermore, upregulation of the PGC‐1α alleviates HG‐induced apoptosis in pancreatic β cells. We also expounded that HG‐activated phosphorylation of nuclear factor‐κB through increasing PGC‐1α expression. Conclusion We verified the function and mechanism of CHOP and provide evidence that CHOP and PGC‐1α may serve as potential candidates for the clinical treatment of DM.