title: α-cell role in β-cell generation and regeneration.
abstract: 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.
authors: Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA, USA. jhabener@partners.org
authors: Joel F
authors: JF
authors: Habener
authors: Violeta
authors: V
authors: Stanojevic
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D052216:Glucagon-Like Peptide 1; D005934:Glucagon