Positive feedback loop between MAPK and aquaporin 7 regulates autophagy and apoptosis induced by palmitate in RIN-m5f cells.

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by peripheral blood insulin resistance and progressive pancreatic β-cell dysfunction which is closely related to apoptosis of β-cells. Aquaporin 7 (AQP7) is the only aquaglyceroporin protein expressed in pancreatic β-cells. However, the relationship between AQP7 and autophagy remains unexplored, with limited studies investigating its link to islet β-cell apoptosis. In our study, we utilized an in vitro model involving palmitate-treated rat pancreatic β-cells (RIN-m5f) to examine these relationships. Our aim was to investigate the effects of AQP7 on autophagy and apoptosis by examining LC3 lipidation levels and p62 expression in pancreatic islet β-cells, thereby elucidating potential underlying mechanisms. Our results showed that phosphorylation of p38 and c-Jun-terminal kinase (JNK) increased in response to palmitate treatment, indicating the activation of these signaling pathways. Conversely, AQP7 expression decreased, reduced autophagy, and promoted apoptosis. AQP7 knockdown activated the p38 and JNK signaling pathways, inhibited autophagy (as evidenced by LC3 lipidation and p62 expression), and increased apoptosis. Furthermore, AQP7 overexpression repressed palmitate-induced apoptosis and alleviated autophagy inhibition by suppressing the p38 and JNK mitogen-activated protein kinase (MAPK) signaling pathways. Our results suggest a positive feedback loop between MAPK signaling and AQP7 that regulates autophagy and apoptosis in RIN-m5f cells under high-fat conditions.