PDF(Pubmed)
Abstract：
Increased insulin level (or \"hyperinsulinemia\") is a common phenomenon in pancreatic ductal adenocarcinoma (PDA) patients and signals poor clinical outcomes. Insulin is safe in low PDA risk population, while insulin significantly promotes PDA risk in high PDA risk population. The correlation between insulin and PDA is a reciprocal self-reinforcing relationship. On the one hand, pancreatic cancer cells synthesize multiple molecules to cause elevated peripheral insulin resistance, thus enhancing hyperinsulinemia. On the other hand, insulin promotes pancreatic cancer initiation and sustains PDA development by eliciting tumorigenic inflammation, regulating lipid and glucose metabolic reprogram, overcoming apoptosis through the crosstalk with IGF-1, stimulating cancer metastasis, and activating tumor microenvironment formation (inflammation, fibrosis, and angiogenesis). Currently, taking glucose sensitizing agents, including metformin, SGLT-2 inhibitor, and GLP-1 agonist, is an effective way of lowering insulin levels and controlling PDA development at the same time. In the future, new drugs targeting insulin-related signal pathways may pave a novel way for suppressing PDA initiation and progression.
摘要：
胰岛素水平升高（或“高胰岛素血症”）是胰腺导管腺癌（PDA）患者的常见现象，表明临床预后不良。胰岛素在低PDA风险人群中是安全的，而在PDA高危人群中,胰岛素显著促进PDA风险.胰岛素和PDA之间的相关性是相互的自我增强关系。一方面,胰腺癌细胞合成多种分子导致外周胰岛素抵抗升高，从而增强高胰岛素血症。另一方面,胰岛素通过引发致瘤性炎症促进胰腺癌的发生和维持PDA的发展，调节脂质和葡萄糖代谢重新编程，通过与IGF-1的串扰克服细胞凋亡，刺激癌症转移，和激活肿瘤微环境的形成（炎症，纤维化，和血管生成）。目前,服用葡萄糖致敏剂，包括二甲双胍,SGLT-2抑制剂,和GLP-1激动剂，是同时降低胰岛素水平和控制PDA发展的有效途径。在未来,针对胰岛素相关信号通路的新药可能为抑制PDA的启动和进展开辟了一条新途径.
