Wang Maoqi, Tan Jiang, He Xueting, Chen Yuqin, Qiu Guoping, Yang Mei
Department of Anatomy, Institute of Neuroscience, College of Basic Medicine, Chongqing Medical University, China.
Institute of Life Science, Chongqing Medical University, China.
FEBS Open Bio. 2025 Jun;15(6):972-984. doi: 10.1002/2211-5463.70011. Epub 2025 Mar 24.
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.
2型糖尿病（T2DM）的特征是外周血胰岛素抵抗和进行性胰腺β细胞功能障碍，这与β细胞凋亡密切相关。水通道蛋白7（AQP7）是胰腺β细胞中唯一表达的水甘油通道蛋白。然而，AQP7与自噬之间的关系尚未得到探索，仅有有限的研究调查了其与胰岛β细胞凋亡的联系。在我们的研究中，我们利用了一个体外模型，该模型涉及用棕榈酸处理的大鼠胰腺β细胞（RIN-m5f）来研究这些关系。我们的目的是通过检测胰岛β细胞中LC3脂化水平和p62表达来研究AQP7对自噬和凋亡的影响，从而阐明潜在的机制。我们的结果表明，棕榈酸处理后p38和c-Jun末端激酶（JNK）的磷酸化增加，表明这些信号通路被激活。相反，AQP7表达降低，自噬减少，凋亡增加。敲低AQP7激活了p38和JNK信号通路，抑制了自噬（通过LC3脂化和p62表达证明），并增加了凋亡。此外，AQP7过表达通过抑制p38和JNK丝裂原活化蛋白激酶（MAPK）信号通路，抑制了棕榈酸诱导的凋亡并减轻了自噬抑制。我们的结果表明，在高脂肪条件下，MAPK信号与AQP7之间存在一个正反馈环，该反馈环调节RIN-m5f细胞中的自噬和凋亡。
