Gezginci-Oktayoglu Selda, Sancar Serap, Karatug-Kacar Ayse, Bolkent Sehnaz
Molecular Biology Section, Biology Department, Faculty of Science, Istanbul University, Vezneciler, 34134, Istanbul, Türkiye.
Protoplasma. 2025 Mar;262(2):341-352. doi: 10.1007/s00709-024-01997-0. Epub 2024 Oct 9.
Pancreatic cell dynamics have important contributions to the development of type 2 diabetes and related diseases such as nonalcoholic fatty pancreas disease. The aim of this study was to investigate the effects of prolonged excessive glucose exposure on the functions of pancreatic beta cells and duct cells in single and co-culture conditions. In this study, we focused on the effects of glucotoxicity on insulin secretion which is the main function of beta cells and on progenitor functions of duct cells. Rat primary INS1 beta cells and ARIP duct cells were exposed to glucose (25 mM) for 72 h under single or indirect co-culture conditions. Glucotoxicity stimuli increased insulin secretion and decreased insulin expression in single beta cells while stimulating beta-cell differentiation and adipogenesis in single duct cells. On the other hand, glucotoxicity caused functional loss and increased proliferation and apoptosis in beta cells while increasing proliferation but suppressed beta-cell differentiation and adipogenesis in duct cells under co-culture conditions. The expression level of miR-335, a microRNA known to be upregulated by leptin and target Runx2, was measured. As a result, unlike single-cell culture, glucotoxicity upregulated miR-335, downregulated Runx2, and decreased insulin signaling in beta cells while downregulating miR-335 and upregulating Runx2, and decreased insulin signaling in duct cells under co-culture conditions. When the results of single and co-culture experiments are compared, insulin and miR-335 may be seen as important mediators for setting up the relation between beta and duct cells. Our findings are important for preventing the development of type 2 diabetes and nonalcoholic fatty pancreas disease, even developing new diagnosis and treatment strategies.
胰腺细胞动态变化对2型糖尿病及相关疾病（如非酒精性脂肪性胰腺疾病）的发展具有重要影响。本研究旨在探讨长期过度葡萄糖暴露在单培养和共培养条件下对胰腺β细胞和导管细胞功能的影响。在本研究中，我们重点关注糖毒性对作为β细胞主要功能的胰岛素分泌以及导管细胞祖细胞功能的影响。大鼠原代INS1β细胞和ARIP导管细胞在单培养或间接共培养条件下暴露于葡萄糖（25 mM）72小时。糖毒性刺激在单培养的β细胞中增加胰岛素分泌并降低胰岛素表达，同时在单培养的导管细胞中刺激β细胞分化和脂肪生成。另一方面，在共培养条件下，糖毒性导致β细胞功能丧失、增殖增加和凋亡增加，同时增加导管细胞的增殖，但抑制β细胞分化和脂肪生成。检测了已知受瘦素上调并靶向Runx2的微小RNA miR-335的表达水平。结果，与单细胞培养不同，在共培养条件下，糖毒性上调β细胞中的miR-335、下调Runx2并降低胰岛素信号传导，同时下调导管细胞中的miR-335、上调Runx2并降低胰岛素信号传导。比较单培养和共培养实验的结果时，胰岛素和miR-335可能被视为建立β细胞与导管细胞之间关系的重要介质。我们的发现对于预防2型糖尿病和非酒精性脂肪性胰腺疾病的发展甚至开发新的诊断和治疗策略具有重要意义。
