New-onset diabetes mellitus has a rough correlation with pancreatic cancer (PaC), but the underlying mechanism remains unclear. This study aimed to explore the exosomal microRNAs and their potential role in PaC-induced β-cell dysfunction. The pancreatic β cells were treated with isolated exosomes from PaC cell lines, SW1990 and BxPC-3, before measuring the glucose-stimulated insulin secretion (GSIS), validating that SW1990 and BxPC-3 might disrupt GSIS of both β cell line MIN6 and primary mouse pancreatic islets. The difference in expression profiles between exosomes and exosome-free medium of PaC cell lines was further defined, revealing that miR-19a secreted by PaC cells might be an important signaling molecule in this process. Furthermore, adenylyl cyclase 1 (Adcy1) and exchange protein directly activated by cAMP 2 (Epac2) were verified as the direct targets of exogenous miR-19a, which was involved in insulin secretion. These results indicated that exosomes might be an important mediator in the pathogenesis of PaC-DM, and miR-19a might be the effector molecule. The findings shed light on the pathogenesis of PaC-DM.

中文翻译：

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胰腺癌衍生的外泌体 microRNA-19a 通过靶向 ADCY1 和 EPAC2 诱导 β 细胞功能障碍

新发糖尿病与胰腺癌（PaC）有大致的相关性，但其潜在机制仍不清楚。本研究旨在探讨外泌体 microRNA 及其在 PaC 诱导的 β 细胞功能障碍中的潜在作用。在测量葡萄糖刺激的胰岛素分泌 (GSIS) 之前，用来自 PaC 细胞系 SW1990 和 BxPC-3 的分离外泌体处理胰腺 β 细胞，验证 SW1990 和 BxPC-3 可能破坏 β 细胞系 MIN6 和原代细胞系的 GSIS小鼠胰岛。进一步确定了PaC细胞系的外泌体和无外泌体培养基之间表达谱的差异，揭示了PaC细胞分泌的miR-19a可能是该过程中的重要信号分子。此外，腺苷酸环化酶 1 (Adcy1) 和直接由 cAMP 2 (Epac2) 激活的交换蛋白被证实是参与胰岛素分泌的外源性 miR-19a 的直接靶标。这些结果表明，外泌体可能是PaC-DM发病机制中的重要介质，而miR-19a可能是效应分子。这些发现揭示了PaC-DM的发病机制。