Academic Journal
Furin may contribute to proglucagon processing and glucagon-like Peptide-1 production in human alpha cells.
| Τίτλος: | Furin may contribute to proglucagon processing and glucagon-like Peptide-1 production in human alpha cells. |
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| Συγγραφείς: | Koepke J; Department of Pharmacology and the Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada., Long W; Department of Pharmacology and the Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada., Barr A; Department of Pharmacology and the Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada., Light PE; Department of Pharmacology and the Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6G 2E1, Canada. Electronic address: plight@ualberta.ca. |
| Πηγή: | Molecular metabolism [Mol Metab] 2025 Dec; Vol. 102, pp. 102259. Date of Electronic Publication: 2025 Sep 27. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2212-8778 (Electronic) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [München] : Elsevier GmbH, 2012- |
| Ιατρικοί όροι (MeSH): | Glucagon-Like Peptide 1*/metabolism , Glucagon-Like Peptide 1*/biosynthesis , Furin*/metabolism , Furin*/genetics , Glucagon-Secreting Cells*/metabolism , Proglucagon*/metabolism, Glucagon/metabolism ; Proprotein Convertase 1/metabolism ; Humans ; Cells, Cultured ; Cell Line |
| Περίληψη: | Objectives: While glucagon-like peptide-1 (GLP-1) production has been previously documented in human alpha cells, the steps regulating its production and secretion are poorly characterized. We investigated the enzymes implicated in proglucagon processing, characterizing their expression and localization in primary human alpha cells and αTC1/9 cells. Methods: Human alpha cells and αTC1/9 cells were maintained in control conditions or exposed to proinflammatory and Akt-activating stimuli to enhance GLP-1 levels. Proglucagon and convertase enzyme gene expression, protein content, and subcellular localization were evaluated by qPCR, Western Blot, and immunofluorescent microscopy, respectively. Results: Our data suggests that the canonical GLP-1-producing enzyme, Prohormone Convertase 1/3 (PC1/3), is poorly expressed and localized in alpha cells, while its homologue furin is optimally positioned for GLP-1 production. We also note that GLP-1 and glucagon processing occur in different subcellular compartments, creating two distinct pools of secretory granules which respond to similar secretory stimuli. Conclusion: Our study suggests that furin, rather than PC1/3, is positioned to process proglucagon into GLP-1, and despite coming from the same precursor molecule, GLP-1 and glucagon are separately packaged in primary human alpha cells. (Copyright © 2025 The Author(s). Published by Elsevier GmbH.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter E. Light reports financial support and administrative support were provided by Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Furin; GLP-1; Islet; PC1/3; Proglucagon |
| Substance Nomenclature: | 89750-14-1 (Glucagon-Like Peptide 1) EC 3.4.21.75 (Furin) 55963-74-1 (Proglucagon) EC 3.4.21.75 (FURIN protein, human) 9007-92-5 (Glucagon) EC 3.4.21.93 (Proprotein Convertase 1) |
| Entry Date(s): | Date Created: 20250929 Date Completed: 20251113 Latest Revision: 20261022 |
| Update Code: | 20261023 |
| PubMed Central ID: | PMC12547723 |
| DOI: | 10.1016/j.molmet.2025.102259 |
| PMID: | 41022304 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2212-8778 |
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| DOI: | 10.1016/j.molmet.2025.102259 |