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活体成像揭示了体内胰岛中葡萄糖依赖性纤毛运动。

Intravital imaging reveals glucose-dependent cilia movement in pancreatic islets in vivo.

作者信息

Melnyk Olha, Guo Jeff Kaihao, Li Zipeng Alex, Jo Jeong Hun, Hughes Jing W, Linnemann Amelia K

机构信息

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.

出版信息

Metabolism. 2025 Feb;163:156105. doi: 10.1016/j.metabol.2024.156105. Epub 2024 Dec 10.

DOI:10.1016/j.metabol.2024.156105
PMID:39667431
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11718731/
Abstract

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.

摘要

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。

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Intravital imaging reveals glucose-dependent cilia movement in pancreatic islets in vivo.活体成像揭示了体内胰岛中葡萄糖依赖性纤毛运动。
Metabolism. 2025 Feb;163:156105. doi: 10.1016/j.metabol.2024.156105. Epub 2024 Dec 10.
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引用本文的文献

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本文引用的文献

1
Structure, interaction and nervous connectivity of beta cell primary cilia.β 细胞初级纤毛的结构、相互作用和神经连接。
Nat Commun. 2024 Oct 24;15(1):9168. doi: 10.1038/s41467-024-53348-5.
2
Lipid droplets sequester palmitic acid to disrupt endothelial ciliation and exacerbate atherosclerosis in male mice.脂滴隔离棕榈酸,破坏内皮纤毛摆动,加剧雄性小鼠动脉粥样硬化。
Nat Commun. 2024 Sep 27;15(1):8273. doi: 10.1038/s41467-024-52621-x.
3
Immuno-scanning electron microscopy of islet primary cilia.胰岛初级纤毛的免疫扫描电子显微镜观察。
J Cell Sci. 2024 Oct 15;137(20). doi: 10.1242/jcs.262038. Epub 2024 May 28.
4
Genetic risk converges on regulatory networks mediating early type 2 diabetes.遗传风险集中于调节早期 2 型糖尿病的网络。
Nature. 2023 Dec;624(7992):621-629. doi: 10.1038/s41586-023-06693-2. Epub 2023 Dec 4.
5
Scanning electron microscopy of human islet cilia.人胰岛纤毛的扫描电子显微镜观察。
Proc Natl Acad Sci U S A. 2023 May 30;120(22):e2302624120. doi: 10.1073/pnas.2302624120. Epub 2023 May 19.
6
The β-cell primary cilium is an autonomous Ca2+ compartment for paracrine GABA signaling.β 细胞初级纤毛是旁分泌 GABA 信号的自主 Ca2+ 隔室。
J Cell Biol. 2023 Jan 2;222(1). doi: 10.1083/jcb.202108101. Epub 2022 Nov 9.
7
Fluorescence imaging of beta cell primary cilia.β 细胞初级纤毛的荧光成像。
Front Endocrinol (Lausanne). 2022 Sep 23;13:1004136. doi: 10.3389/fendo.2022.1004136. eCollection 2022.
8
Islet primary cilia motility controls insulin secretion.胰岛初级纤毛运动控制胰岛素分泌。
Sci Adv. 2022 Sep 23;8(38):eabq8486. doi: 10.1126/sciadv.abq8486.
9
Palmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism.软脂酸通过自噬依赖性机制控制纤毛生成,从而调节下丘脑神经元中的胰岛素信号传导。
Cell Death Dis. 2022 Jul 28;13(7):659. doi: 10.1038/s41419-022-05109-9.
10
An open-access volume electron microscopy atlas of whole cells and tissues.开放获取的全细胞和组织电子显微镜图谱集
Nature. 2021 Nov;599(7883):147-151. doi: 10.1038/s41586-021-03992-4. Epub 2021 Oct 6.