Melnyk Olha, Guo Jeff Kaihao, Li Zipeng Alex, Jo Jeong Hun, Hughes Jing W, Linnemann Amelia K
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA.
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, USA; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, USA.
Metabolism. 2025 Feb;163:156105. doi: 10.1016/j.metabol.2024.156105. Epub 2024 Dec 10.
Pancreatic islet cells harbor primary cilia, small sensory organelles that detect environmental changes to regulate hormone secretion and intercellular communication. While the sensory and signaling capacity of primary cilia are well-appreciated, it is less recognized that these organelles also possess active motility, including in dense multicellular tissues such as the pancreatic islet. In this manuscript, we use transgenic cilia reporter mice and an intravital imaging approach to quantitate primary cilia dynamics as it occurs in live mouse pancreatic islets. We validate this imaging workflow as suitable for studying islet cilia motion in real time in vivo and demonstrate that glucose stimulation corresponds to a change in cilia motility, which may be a physiologic measure of nutrient-dependent fluxes in islet cell function. Complementary ex vivo analysis of isolated islets further demonstrates that metabolic stress in the form of lipotoxicity impairs cilia motility and these effects can be reversed by glucose elevation. These findings suggest that cilia motility is sensitive to metabolic stress and highlight its potential functional role in beta cell adaptation.
胰岛细胞含有初级纤毛,这是一种小型感觉细胞器,可检测环境变化以调节激素分泌和细胞间通讯。虽然初级纤毛的感觉和信号传导能力已得到充分认识,但人们较少认识到这些细胞器也具有主动运动能力,包括在胰岛等密集的多细胞组织中。在本论文中,我们使用转基因纤毛报告小鼠和活体成像方法来定量在活小鼠胰岛中发生的初级纤毛动态变化。我们验证了这种成像工作流程适用于在体内实时研究胰岛纤毛运动,并证明葡萄糖刺激与纤毛运动性的变化相对应,这可能是胰岛细胞功能中营养物质依赖性通量的一种生理指标。对分离胰岛的补充离体分析进一步表明,脂毒性形式的代谢应激会损害纤毛运动,而葡萄糖浓度升高可逆转这些影响。这些发现表明纤毛运动对代谢应激敏感,并突出了其在β细胞适应中的潜在功能作用。