TY - JOUR AB - Vanin‑1 (VNN1) may be a potential biomarker for the early screening of pancreatic cancer (PC)‑associated diabetes (PCAD). A previous study by the authors reported that cysteamine secreted by VNN1‑overexpressing PC cells induced the dysfunction of paraneoplastic insulinoma cell lines by increasing oxidative stress. In the present study, it was observed that both cysteamine and exosomes (Exos) secreted by VNN1‑overexpressing PC cells aggravated the dysfunction of mouse primary islets. PC‑derived VNN1 could be transported into islets through PC cell‑derived Exos (PC‑Exos). However, β‑cell dedifferentiation, and not cysteamine‑mediated oxidative stress, was responsible for the islet dysfunction induced by VNN1‑containing Exos. VNN1 inhibited the phosphorylation of AMPK and GAPDH, and prevented Sirt1 activation and FoxO1 deacetylation in islets, which may be responsible for the induction of β‑cell dedifferentiation induced by VNN1‑overexpressing PC‑Exos. Furthermore, it was demonstrated that VNN1‑overexpressing PC cells further impaired the functions of paraneoplastic islets in vivo using diabetic mice with islets transplanted under the kidney capsule. On the whole, the present study demonstrates that PC cells overexpressing VNN1 exacerbate the dysfunction of paraneoplastic islets by inducing oxidative stress and β‑cell dedifferentiation. AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China AU - Qin,Wenjie AU - Kang,Muxing AU - Li,Chao AU - Zheng,Wen AU - Guo,Qingqu DA - 2023/06/01 DO - 10.3892/or.2023.8557 IS - 6 JO - Oncol Rep KW - VNN1 pancreatic cancer‑associated diabetes oxidative stress exosomes β‑cell dedifferentiation PY - 2023 SN - 1021-335X 1791-2431 SP - 120 ST - VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation T2 - Oncology Reports TI - VNN1 overexpression in pancreatic cancer cells inhibits paraneoplastic islet function by increasing oxidative stress and inducing β‑cell dedifferentiation UR - https://doi.org/10.3892/or.2023.8557 VL - 49 ER -