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Home Search Quick Search Advanced Fulltext Browse Collections Persons My eDoc Session History Login Name: Password: Documentation Help Support Wiki Direct access to document ID:	Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents ID: 723900.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016 Glucagon is essential for alpha cell transdifferentiation and beta cell neogenesis Authors: Ye, L.; Robertson, M. A.; Hesselson, D.; Stainier, D. Y.; Anderson, R. M. Date of Publication (YYYY-MM-DD): 2015-04-15 Title of Journal: Development Volume: 142 Issue / Number: 8 Start Page: 1407 End Page: 1417 Audience: Not Specified Abstract / Description: The interconversion of cell lineages via transdifferentiation is an adaptive mode of tissue regeneration and an appealing therapeutic target. However, its clinical exploitation is contingent upon the discovery of contextual regulators of cell fate acquisition and maintenance. In murine models of diabetes, glucagon-secreting alpha cells transdifferentiate into insulin-secreting beta cells following targeted beta cell depletion, regenerating the form and function of the pancreatic islet. However, the molecular triggers of this mode of regeneration are unknown. Here, using lineage-tracing assays in a transgenic zebrafish model of beta cell ablation, we demonstrate conserved plasticity of alpha cells during islet regeneration. In addition, we show that glucagon expression is upregulated after injury. Through gene knockdown and rescue approaches, we also find that peptides derived from the glucagon gene are necessary for alpha-to-beta cell fate switching. Importantly, whereas beta cell neogenesis was stimulated by glucose, alpha-to-beta cell conversion was not, suggesting that transdifferentiation is not mediated by glucagon/GLP-1 control of hepatic glucose production. Overall, this study supports the hypothesis that alpha cells are an endogenous reservoir of potential new beta cells. It further reveals that glucagon plays an important role in maintaining endocrine cell homeostasis through feedback mechanisms that govern cell fate stability. Free Keywords: Animals; Animals, Genetically Modified; Cell Proliferation/physiology; Cell Transdifferentiation/physiology; Glucagon/*metabolism; Glucagon-Like Peptide 1/metabolism; Glucagon-Secreting Cells/*cytology/*metabolism; Insulin-Secreting Cells/*cytology/*metabolism; Pancreas/cytology/metabolism; Zebrafish; Alpha cell; Arx; Arxa; Beta cell; Glp-1; Gcga; Glucagon; Insulin; Pancreas; Pancreatic progenitor; Regeneration; Transdifferentiation External Publication Status: published Document Type: Article Communicated by: n.n. Affiliations: MPI für physiologische und klinische Forschung External Affiliations: Department of Biochemistry and Biophysics, 1550 4th Street Rock Hall Room 381, University of California San Francisco, San Francisco, CA 94143, USA. Wells Center for Pediatric Research and Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Van Nuys Medical Sciences Building MS2053, Indianapolis, IN 46202, USA ryanande@iu.edu. Identifiers: ISSN:1477-9129 (Electronic) 0950-1991 (Linking) %R 10.1242/dev.117911 URL:http://www.ncbi.nlm.nih.gov/pubmed/25852199 The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.