Review
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World J Diabetes. Dec 15, 2014; 5(6): 847-853
Published online Dec 15, 2014. doi: 10.4239/wjd.v5.i6.847
Transdifferentiation of pancreatic α-cells into insulin-secreting cells: From experimental models to underlying mechanisms
Jieli Lu, Rami Jaafer, Rémy Bonnavion, Philippe Bertolino, Chang-Xian Zhang
Jieli Lu, Chang-Xian Zhang, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China
Jieli Lu, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China
Rami Jaafer, Rémy Bonnavion, Philippe Bertolino, Chang-Xian Zhang, Inserm U1052, Cancer Research Centre of Lyon, F-69008 Lyon, France
Rami Jaafer, Rémy Bonnavion, Philippe Bertolino, Chang-Xian Zhang, CNRS UMR5286, Cancer Research Centre of Lyon, F-69008 Lyon, France
Rami Jaafer, Rémy Bonnavion, Philippe Bertolino, Chang Xian Zhang, Cancer Research Centre of Lyon, Université de Lyon, F-69008 Lyon, France
Author contributions: Lu J, Jaafer R, Bonnavion R, Bertolino P and Zhang CX contributed to the research and the discussion; Lu J and Zhang CX wrote the paper.
Supported by The Agence National de Recherche (ANR 2010 BLAN 1240 01), the Ligue contre le Cancer du Rhône and de la Loire; the CMIRA program of Region Rhône-Alpes, No. 12004959-01; the Fondation ARC pour la Recherche sur le Cancer, France, No. SFI20101201530; National Nature Science Foundation of China, No. NSFC81170719, No. 81370960; and Shanghai New Excellent Youth Program, No. XYQ2011009
Correspondence to: Jieli Lu, MD, PhD, Sino-French Life Science and Genomic Center, the E-Institute of Shanghai, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University, Xuhui District, Shanghai 200025, China. jielilu@hotmail.com
Telephone: +86-21-64370045 Fax: +86-21-64749885
Received: November 27, 2013
Revised: July 19, 2014
Accepted: July 27, 2014
Published online: December 15, 2014
Abstract

Pancreatic insulin-secreting β-cells are essential regulators of glucose metabolism. New strategies are currently being investigated to create insulin-producing β cells to replace deficient β cells, including the differentiation of either stem or progenitor cells, and the newly uncovered transdifferentiation of mature non-β islet cell types. However, in order to correctly drive any cell to adopt a new β-cell fate, a better understanding of the in vivo mechanisms involved in the plasticity and biology of islet cells is urgently required. Here, we review the recent studies reporting the phenomenon of transdifferentiation of α cells into β cells by focusing on the major candidates and contexts revealed to be involved in adult β-cell regeneration through this process. The possible underlying mechanisms of transdifferentiation and the interactions between several key factors involved in the process are also addressed. We propose that it is of importance to further study the molecular and cellular mechanisms underlying α- to β-cell transdifferentiation, in order to make β-cell regeneration from α cells a relevant and realizable strategy for developing cell-replacement therapy.

Keywords: α-cell, β-cell, Transdifferentiation, Diabetes mellitus, Cell-replacement therapy

Core tip: Recent works highlighted the phenomenon of transdifferentiation of pancreatic α cells into β cells, which has drawn much attention in the field. Considering that α-cell transdifferentiation could be used as a new strategy of cell replacement therapy for the treatment of diabetes, because of the presence of α cells in the pancreas of both type 1 and 2 diabetics, we believe that it is relevant to elucidate the cellular and molecular events in α- to β-cell conversion. Our review focuses on the recent experimental α-cell transdifferentiation models, highlighting the insight provided by these works into the candidates and contexts revealed to be involved in this process.