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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 沈湯龍 | zh_TW |
| dc.contributor.advisor | Tang-Long Shen | en |
| dc.contributor.author | 葉哲宇 | zh_TW |
| dc.contributor.author | Che-Yu Yeh | en |
| dc.date.accessioned | 2025-02-27T16:17:44Z | - |
| dc.date.available | 2025-02-28 | - |
| dc.date.copyright | 2025-02-27 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-02-11 | - |
| dc.identifier.citation | Ahmed, A. J., Majeed, S. R., & Obaid, H. M. (2020). Biochemistry and molecular cell biology of diabetic complications. Syst. Rev. Pharm, 11, 850-860.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/97122 | - |
| dc.description.abstract | 糖尿病是現代人最常見的疾病之一，也是台灣十大死因之一。糖尿病的長期高血糖導致許多的併發症，如周邊神經病變和視網膜病變等。本研究探討了細胞外葡萄糖濃度對脂肪細胞分化及其來源外泌體對視網膜與神經細胞的生物影響和其在糖尿病併發症中的潛在作用。將 C3H10T1/2 細胞分別在低（5.5 mM）及高（30 mM）葡萄糖條件下分化，結果顯示高葡萄糖濃度顯著促進脂質累積及脂肪細胞生成相關基因的表達，代表葡萄糖是脂肪細胞生成的重要調控因子之一，而從這些脂肪細胞中分離的外泌體無論葡萄糖濃度在結構上並無太大差異。然而，功能測試顯示，高葡萄糖來源的外泌體顯著增加了 ARPE-19 細胞的氧化壓力並損害其線粒體功能，同時也縮短了 SH-SY5Y 細胞的神經突觸。
外泌體蛋白質體學分析結合患者來源數據揭示了與炎症、氧化壓力及細胞外基質重塑相關的通路，例如趨化因子信號傳導路徑及 NF-κB 活化，這些路徑在糖尿病併發症的進展中發揮重要作用，包括視網膜和神經損傷。Seahorse XF 分析進一步顯示，高葡萄糖來源的外泌體降低了 ARPE-19 細胞的線粒體呼吸作用的能力，而在SH-SY5Y 細胞上則未有顯著差異，代表不同細胞類型對外泌體造成的代謝調節具有不同的敏感性。綜上所述，本研究闡明了高血糖如何改變脂肪細胞外泌體功能，將代謝失調與糖尿病併發症的發病機制連結，並提供了減輕這些影響的潛在治療方向。 | zh_TW |
| dc.description.abstract | Diabetes mellitus is among the most common illnesses among modern humans and ranks as one of the top ten causes of death in Taiwan. Long-term hyperglycemia in diabetes leads to various complications such as peripheral neuropathy and retinopathy. This study explores the influence of extracellular glucose levels on adipocyte differentiation and the biological effects of adipocyte-derived exosomes on retinal and neuronal cells, highlighting their potential roles in diabetic complications. C3H10T1/2 cells were differentiated under low (5.5 mM) and high (30 mM) glucose conditions, revealing that high glucose concentrations significantly enhanced lipid accumulation and the expression of adipogenic genes, underscoring glucose as a critical regulator of adipogenesis. Exosomes isolated from these adipocytes were characterized and shown to retain structural consistency regardless of glucose levels. However, functional assays indicated that exosomes from high glucose conditions increased oxidative stress and impaired mitochondrial function in ARPE-19 cells while reducing neurite outgrowth in SH-SY5Y cells, without significantly affecting their mitochondrial function.
Proteomic analysis of exosome cargo, combined with patient-derived exosome data, identified pathways related to inflammation, oxidative stress, and extracellular matrix remodeling, such as the chemokine signaling pathway and NF-κB activation. These pathways are implicated in the progression of diabetic complications, including retinal and neural damage. Seahorse XF analysis further revealed that high glucose-derived exosomes reduced mitochondrial spare respiratory capacity in ARPE-19 cells, suggesting a cell-type-specific vulnerability to exosome-mediated metabolic dysregulation. Collectively, these findings provide insights into the mechanisms by which hyperglycemia alters adipocyte-derived exosome function, linking metabolic dysregulation to the pathogenesis of diabetic complications and offering potential therapeutic targets to mitigate these effects. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-27T16:17:44Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-27T16:17:44Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 摘要 II
Abstract III TABLE OF CONTENTS V LIST OF TABLES VIII LIST OF FIGURES IX 1.Introduction 1 2. Materials & Methods 7 2.1 Cell culture and adipocyte differentiation 7 2.2 Oil Red O staining and quantification 8 2.3 Exosome isolation 9 2.4 Nanoparticle Tracking Analysis (NTA) 9 2.5 Negative staining and transmission electron microscopy 10 2.6 Protein isolation and western blot 10 2.7 Exosome staining 11 2.8 Cell viability assay 12 2.9 SH-SY5Y differentiation and nerve fiber length calculation 12 2.10 ROS detection and immunostaining 13 2.11 Protein Identification 14 2.12 Seahorse Assay 17 2.13 Data Analysis and Image Processing 17 3. Result 19 3.1 Extracellular glucose levels significantly influence adipocyte differentiation 19 3.2 Characterization of exosomes derived from adipocytes differentiated under variable glucose conditions 20 3.3 Assessment of adipocyte-derived exosome uptake by retinal and neuronal cells 21 3.4 Effects of high glucose-derived exosomes on cell viability and proliferation 21 3.5 High glucose-derived exosomes impair neurite outgrowth 22 3.6 Biological pathways linking exosome from patient serum and adipocyte to diabetic complications 23 3.7 High glucose-derived exosomes induce elevated oxidative stress in retinal and neuronal cells 25 3.8 Differential effects of adipocyte-derived exosomes on SH-SY5Y and ARPE-19 mitochondrial function revealed by Seahorse XF Analysis 25 4. Discussion 29 5. Conclusion 42 6. References 43 Tables 48 Figures 56 Supplement Data 76 Figure S1. Heatmap of adipocyte-derived exosome 76 Figure S2. GSEA Analysis of LG vs UN 77 Figure S3. GSEA Analysis of HG vs UN 78 Figure S4. GSEA Analysis of HG vs LG 79 | - |
| dc.language.iso | en | - |
| dc.subject | 脂肪細胞 | zh_TW |
| dc.subject | 蛋白質體學 | zh_TW |
| dc.subject | 神經病變 | zh_TW |
| dc.subject | 視網膜病變 | zh_TW |
| dc.subject | 外泌體 | zh_TW |
| dc.subject | 糖尿病 | zh_TW |
| dc.subject | neuropathy | en |
| dc.subject | adipocyte | en |
| dc.subject | retinopathy | en |
| dc.subject | exosome | en |
| dc.subject | proteomics | en |
| dc.subject | Diabetes mellitus | en |
| dc.title | 探討高葡萄糖誘導脂肪細胞外泌體於視網膜及神經病變之角色 | zh_TW |
| dc.title | The role of high glucose induced adipocyte exosomes in neuropathy/retinopathy | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 周涵怡;丁詩同;黃舒宜 | zh_TW |
| dc.contributor.oralexamcommittee | Han-Yie Chou;Shih-Torng Ding;Shu-Yi Huang | en |
| dc.subject.keyword | 糖尿病,脂肪細胞,外泌體,視網膜病變,神經病變,蛋白質體學, | zh_TW |
| dc.subject.keyword | Diabetes mellitus,exosome,adipocyte,retinopathy,neuropathy,proteomics, | en |
| dc.relation.page | 79 | - |
| dc.identifier.doi | 10.6342/NTU202500597 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2025-02-12 | - |
| dc.contributor.author-college | 生物資源暨農學院 | - |
| dc.contributor.author-dept | 植物病理與微生物學系 | - |
| dc.date.embargo-lift | 2030-02-10 | - |
| 顯示於系所單位： | 植物病理與微生物學系 | |
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