Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Fabrizio Thorel,Virginie Nepote,Isabelle Avril,Kenji Kohno,Renaud Desgraz,Simona Chera,Pedro Luis Herrera +6 more
TLDR
In this article, a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation was used to investigate whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total β-cell loss, as in diabetes.Abstract:
Pancreatic insulin-producing beta-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, beta-cell loss). It is not known whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total beta-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-beta-cell) source. Here we show beta-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation. If given insulin, the mice survived and showed beta-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing alpha-cells before beta-cell ablation tracked large fractions of regenerated beta-cells as deriving from alpha-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing beta-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.read more
Citations
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Heterogenous impairment of α cell function in type 2 diabetes is linked to cell maturation state.
Xiao-Qing Dai,Joan Camunas-Soler,Linford J.B. Briant,Theodore dos Santos,Aliya F. Spigelman,Emily M. Walker,Rafael Arrojo e Drigo,Austin Bautista,Robert C. Jones,Dana Avrahami,James Lyon,Aifang Nie,Nancy Smith,Yongneng Zhang,Janyne Johnson,Jocelyn E. Manning Fox,Evangelos D. Michelakis,Peter E. Light,Klaus H. Kaestner,Seung K. Kim,Patrik Rorsman,Roland Stein,Stephen R. Quake,Patrick E. MacDonald +23 more
TL;DR: In this paper , the authors examined α cells from human donors and mice using electrophysiological, transcriptomic, and computational approaches, and identified links between cell membrane properties and cell surface signaling receptors, mitochondrial respiratory chain complex assembly and cell maturation.
Journal ArticleDOI
Id3 upregulates BrdU incorporation associated with a DNA damage response, not replication, in human pancreatic β-cells
TL;DR: The data establish that loss of p57Kip2 is not sufficient to induce cell cycle entry in adult β-cells, and reveal thatβ-cells possess intrinsic resistance to cell cycle Entry not common to all quiescent epithelial cells in the adult human pancreas.
Journal ArticleDOI
Obestatin enhances in vitro generation of pancreatic islets through regulation of developmental pathways.
lessandra Baragli,Cristina Grande,Iacopo Gesmundo,Fabio Settanni,Marina Taliano,Davide Gallo,Eleonora Gargantini,Ezio Ghigo,Riccarda Granata +8 more
TL;DR: Results indicate that obestatin improves the generation of functional β-cells/ICCs in vitro, suggesting implications for cell-based replacement therapy in diabetes and may play a role in regulating pathways involved in pancreas development and regeneration.
Journal ArticleDOI
Development of the endocrine pancreas and novel strategies for β-cell mass restoration and diabetes therapy
A.L. Márquez-Aguirre,Alejandro A. Canales-Aguirre,Eduardo Padilla-Camberos,Hugo Esquivel-Solís,N.E. Díaz-Martínez +4 more
TL;DR: Two possible approaches of β- cell mass restoration for diabetes mellitus therapy are discussed: β-cell regeneration andβ-cell replacement, which are critically analyzed with respect to the accessibility of the cells, potential risk to patients, and possible clinical outcomes.
Journal ArticleDOI
Role of adenosine signalling and metabolism in β-cell regeneration.
TL;DR: In this review, both intracellular and extracellular mechanisms of adenosine and ATP are discussed in terms of their established and putative effects on β-cell regeneration.
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