Document Detail

α-cell role in β-cell generation and regeneration.
MedLine Citation:
PMID:  22847495     Owner:  NLM     Status:  MEDLINE    
This review considers the role of α-cells in β-cell generation and regeneration. We present recent evidence obtained from lineage-tracing studies showing that α-cells can serve as progenitors of β-cells and present a hypothetical model how injured β-cells might activate α-cells in adult islets to promote β-cell regeneration. β-cells appear to arise by way of their trans-differentiation from undifferentiated α progenitor cells, pro-α-cells, both during embryonic development of the islets and in the adult pancreas in response to β-cell injuries. Plasticity of α-cells is endowed by the expression of the gene encoding proglucagon, a prohormone that can give rise to glucagon and glucagon-like peptides (GLPs). The production of glucagon from proglucagon is characteristic of fully-differentiated α-cells whereas GLP-1 is a product of undifferentiated α-cells. GLP-1, a cell growth and survival factor, is proposed to promote the expansion of neurogenin3-expressing, undifferentiated pro-α-cells during development. β-cells arise from pro-α-cells by a change in the relative amounts of the transcription factors Arx and Pax4, master regulators of the α- and β-cell lineages, respectively. A paracrine/autocrine model is proposed whereby injuries of β-cells in adult islets induce the production and release of factors, such as stromal cell-derived factor-1, that cause the de-differentiation of adjacent α-cells into pro-α-cells. Pro-α-cells produce GLP-1 and its receptor that renders them competent to trans-differentiate into β-cells. The trans-differentiation of pro-α-cells into β-cells provides a potentially exploitable mechanism for the regeneration of β-cells in individuals with type 1 diabetes.
Joel F Habener; Violeta Stanojevic
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Islets     Volume:  4     ISSN:  1938-2022     ISO Abbreviation:  Islets     Publication Date:    2012 May-Jun
Date Detail:
Created Date:  2012-07-31     Completed Date:  2013-03-08     Revised Date:  2014-10-09    
Medline Journal Info:
Nlm Unique ID:  101495366     Medline TA:  Islets     Country:  United States    
Other Details:
Languages:  eng     Pagination:  188-98     Citation Subset:  IM    
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MeSH Terms
Cell Differentiation / physiology
Glucagon / metabolism
Glucagon-Like Peptide 1 / metabolism
Glucagon-Secreting Cells / cytology,  metabolism,  physiology*
Insulin-Secreting Cells / cytology,  metabolism,  physiology*
Islets of Langerhans / cytology,  metabolism,  physiology*
Regeneration / physiology*
Signal Transduction
Stem Cells / cytology,  metabolism
Reg. No./Substance:
89750-14-1/Glucagon-Like Peptide 1; 9007-92-5/Glucagon

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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