IF 10.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Metabolism: clinical and experimental Pub Date : 2025-02-01 Epub Date: 2024-12-10 DOI:10.1016/j.metabol.2024.156105
Olha Melnyk, Jeff Kaihao Guo, Zipeng Alex Li, Jeong Hun Jo, Jing W Hughes, Amelia K Linnemann
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引用次数: 0

摘要

胰岛细胞含有初级纤毛,这种小型感觉细胞器能检测环境变化,从而调节激素分泌和细胞间通信。初级纤毛的感觉和信号传导能力已得到广泛认可,但人们较少认识到这些细胞器还具有主动运动能力,包括在胰岛等致密多细胞组织中。在本手稿中,我们利用转基因纤毛报告小鼠和眼内成像方法对活体小鼠胰岛中的初级纤毛动态进行了量化。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,并证明葡萄糖刺激对应于纤毛运动的变化,而纤毛运动可能是胰岛细胞功能中营养依赖性通量的生理指标。对离体胰岛的体外补充分析进一步证明,脂毒性形式的代谢压力会损害纤毛运动,而葡萄糖升高可逆转这些影响。这些研究结果表明,纤毛运动对代谢压力很敏感,并强调了它在β细胞适应过程中的潜在功能作用。
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Intravital imaging reveals glucose-dependent cilia movement in pancreatic islets in vivo.

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.

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来源期刊
Metabolism: clinical and experimental
Metabolism: clinical and experimental 医学-内分泌学与代谢
CiteScore
18.90
自引率
3.10%
发文量
310
审稿时长
16 days
期刊介绍: Metabolism upholds research excellence by disseminating high-quality original research, reviews, editorials, and commentaries covering all facets of human metabolism. Consideration for publication in Metabolism extends to studies in humans, animal, and cellular models, with a particular emphasis on work demonstrating strong translational potential. The journal addresses a range of topics, including: - Energy Expenditure and Obesity - Metabolic Syndrome, Prediabetes, and Diabetes - Nutrition, Exercise, and the Environment - Genetics and Genomics, Proteomics, and Metabolomics - Carbohydrate, Lipid, and Protein Metabolism - Endocrinology and Hypertension - Mineral and Bone Metabolism - Cardiovascular Diseases and Malignancies - Inflammation in metabolism and immunometabolism
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