脂肪细胞来源的细胞外囊泡通过转运促胰岛素蛋白货物增加胰岛素分泌,Nature Communications

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脂肪细胞来源的细胞外囊泡通过转运促胰岛素蛋白货物增加胰岛素分泌
Nature Communications ( IF 14.7 ) Pub Date : 2023-02-09 , DOI: 10.1038/s41467-023-36148-1
Konxhe Kulaj _{1,

2,

3} , Alexandra Harger _{1,

2} , Michaela Bauer _{1,

2,

3} , Özüm S Caliskan _{1,

2} , Tilak Kumar Gupta ₄ , Dapi Menglin Chiang ₅ , Edward Milbank _{1,

3} , Josefine Reber ₆ , Angelos Karlas _{6,

7,

8,

9} , Petra Kotzbeck _{1,

10} , David N Sailer _{1,

11} , Francesco Volta _{12,

13} , Dominik Lutter _{1,

2} , Sneha Prakash _{1,

2} , Juliane Merl-Pham ₁₄ , Vasilis Ntziachristos _{6,

7,

9} , Hans Hauner _{15,

16} , Michael W Pfaffl ₅ , Matthias H Tschöp _{1,

2,

17} , Timo D Müller _{1,

2} , Stefanie M Hauck ₁₄ , Benjamin D Engel _{18,

19} , Jantje M Gerdes ₁₂ , Paul T Pfluger _{1,

2,

20,

21} , Natalie Krahmer _{1,

2} , Kerstin Stemmer _{1,

2,

3}

Affiliation

Institute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany.
German Center for Diabetes Research (DZD), Neuherberg, Germany.
Molecular Cell Biology, Institute for Theoretical Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany.
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Munich, Germany.
Institute of Biological and Medical Imaging, Helmholtz Zentrum München, Neuherberg, Germany.
Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.
Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
Department of Surgery, Division of Plastic, Aesthetic and Reconstructive Surgery, Medical University of Graz, Graz, Austria.
Institute of Molecular Oncology and Functional Genomics, School of Medicine, Technical University of Munich, Munich, Germany.
Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany.
Department of Medicine and Surgery, University of Parma, Parma, Italy.
Metabolomics and Proteomics Core, Helmholtz Zentrum München, Neuherberg, Germany.
Institute for Nutritional Medicine, School of Medicine, Technical University of Munich, Munich, Germany.
ZIEL-Institute for Food & Health, Technical University of Munich, Freising, Germany.
Division of Metabolic Diseases, Department of Medicine, Technical University of Munich, Munich, Germany.
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany.
Biozentrum, University of Basel, Basel, Switzerland.
Research Unit NeuroBiology of Diabetes, Helmholtz Zentrum München, Neuherberg, Germany.
Chair of Neurobiology of Diabetes, TUM School of Medicine, Technical University of Munich, Munich, Germany.

脂肪细胞来源的细胞外囊泡 (AdEVs) 是膜状纳米颗粒，可将脂肪组织与其他器官的通讯传递出去。在这里，为了描述它们作为具有葡萄糖调节性质的信使的作用，我们将荧光 AdEV 示踪和 SILAC 标记与（磷酸）蛋白质组学配对，并揭示 AdEV 将功能性促胰岛素蛋白货物转移到胰腺 β 细胞中。转移后，AdEV 蛋白被磷酸化，通过增加总蛋白丰度和磷酸位点动力学增强促胰岛素 GPCR/cAMP/PKA 信号，并最终增强小鼠胰岛中的第一阶段葡萄糖刺激胰岛素分泌 (GSIS)。值得注意的是，促胰岛素作用仅限于从肥胖和胰岛素抵抗的小鼠中分离出来的 AdEV，而不是瘦小鼠，这与差异蛋白质负载和 AdEV 管腔形态一致。同样，用来自肥胖而非瘦小鼠的 AdEV 进行体内预处理可增强小鼠的胰岛素分泌和葡萄糖耐量。该数据表明，分泌的 AdEV 可以告知胰腺 β 细胞脂肪组织中的胰岛素抵抗，以便在胰岛素需求增加时放大 GSIS。

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更新日期：2023-02-09

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