Peptidomics of enteroendocrine cells and characterisation of potential effects of a novel preprogastrin derived-peptide on glucose tolerance in lean mice
| العنوان: | Peptidomics of enteroendocrine cells and characterisation of potential effects of a novel preprogastrin derived-peptide on glucose tolerance in lean mice |
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| المؤلفون: | Anne K. McGavigan, Van B. Lu, Laura Sheldrake, Elise Bernard, Helen Brant, Sam G Galvin, Haidee Pitt, Pierre Larraufie, David Baker, Frank Reimann, Elisabeth O’Flaherty, Carina Ämmälä, Lutz Jermutus, John Hood, Shannon Conder, Geoffrey P. Roberts, Dawn Atherton-Kemp, Richard G. Kay, Fiona M. Gribble |
| المساهمون: | Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge [UK] (CAM), Galvin, Sam [0000-0001-5910-9471], Kay, Richard [0000-0002-3827-8687], Gribble, Fiona [0000-0002-4232-2898], Reimann, Frank [0000-0001-9399-6377], Apollo - University of Cambridge Repository |
| المصدر: | Peptides Peptides, Elsevier, 2021, pp.170532. ⟨10.1016/j.peptides.2021.170532⟩ |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Proteome, Physiology, Enteroendocrine cell, Peptide, Biochemistry, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Mice, 0302 clinical medicine, Endocrinology, Biosynthesis, Thinness, In vivo, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gastrins, Animals, Humans, Protein Precursors, Peptidomics, Gene, Cells, Cultured, chemistry.chemical_classification, Enteroendocrine cells, biology, Mass spectrometry, Chemistry, Progastrin, Chromogranin A, Prohormones, Glucose Tolerance Test, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, In vitro, 3. Good health, Gastrointestinal Tract, 030104 developmental biology, Glucose, Granins, Models, Animal, biology.protein, Peptides, 030217 neurology & neurosurgery, Hormone |
| الوصف: | Highlights • A peptidomic analysis of the human and mouse gastrointestinal tract was performed. • High fat feeding reduced the content of GCG, PYY and INSL5 in the distal colon. • Several interesting novel peptides were synthesised for in vivo characterisation. • A novel product of progastrin modestly improved glucose tolerance in lean mice. Objectives To analyse the peptidomics of mouse enteroendocrine cells (EECs) and human gastrointestinal (GI) tissue and identify novel gut derived peptides. Methods High resolution nano-flow liquid chromatography mass spectrometry (LC–MS/MS) was performed on (i) flow-cytometry purified NeuroD1 positive cells from mouse and homogenised human intestinal biopsies, (ii) supernatants from primary murine intestinal cultures, (iii) intestinal homogenates from mice fed high fat diet. Candidate bioactive peptides were selected on the basis of species conservation, high expression/biosynthesis in EECs and evidence of regulated secretionin vitro. Candidate novel gut-derived peptides were chronically administered to mice to assess effects on food intake and glucose tolerance. Results A large number of peptide fragments were identified from human and mouse, including known full-length gut hormones and enzymatic degradation products. EEC-specific peptides were largely from vesicular proteins, particularly prohormones, granins and processing enzymes, of which several exhibited regulated secretion in vitro. No regulated peptides were identified from previously unknown genes. High fat feeding particularly affected the distal colon, resulting in reduced peptide levels from GCG, PYY and INSL5. Of the two candidate novel peptides tested in vivo, a peptide from Chromogranin A (ChgA 435−462a) had no measurable effect, but a progastrin-derived peptide (Gast p59−79), modestly improved glucose tolerance in lean mice. Conclusion LC–MS/MS peptidomic analysis of murine EECs and human GI tissue identified the spectrum of peptides produced by EECs, including a potential novel gut hormone, Gast p59−79, with minor effects on glucose tolerance. |
| وصف الملف: | application/vnd.openxmlformats-officedocument.wordprocessingml.document; application/vnd.openxmlformats-officedocument.presentationml.presentation; application/vnd.openxmlformats-officedocument.spreadsheetml.sheet |
| اللغة: | English |
| تدمد: | 0196-9781 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f338a4e5b3f1c7620f53189edbfc90c2Test https://hal.archives-ouvertes.fr/hal-03208731/file/1-s2.0-S0196978121000401-main.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f338a4e5b3f1c7620f53189edbfc90c2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 01969781 |
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