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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Journal ArticleDOI
Tissue repair brakes: A common paradigm in the biology of regeneration
TL;DR: The pharmacological or genetic/epigenetic modulation of such regenerative brakes could release a dormant but innate adaptive competence of certain cell types and therefore boost tissue regeneration in different situations.
Journal ArticleDOI
Partners for life.
Lena Eliasson,Anna Wendt +1 more
TL;DR: The hormones insulin and glucagon both play important roles in the development of diabetes and are regulated by the pancreas through a number of mechanisms.
Journal ArticleDOI
Alpha-cell paracrine signaling in the regulation of beta-cell insulin secretion
TL;DR: Recent advances are described and integrated in the understanding of the impact of alpha-cell paracrine signaling on insulin secretory dynamics and how this intra-islet crosstalk more broadly contributes to whole-body glucose regulation in health and under metabolic stress.
Journal ArticleDOI
Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice
Yuko Nakatsuru,Yuko Murase-Mishiba,Megumi Bessho-Tachibana,Jungo Terasaki,Toshiaki Hanafusa,Akihisa Imagawa +5 more
TL;DR: It is suggested that taurine improves glucose tolerance, in spite of its subsequent increased glucagon production, partly by increasing pancreatic β-cells and insulin production in vivo.
Journal ArticleDOI
Targeted Ablation of Pancreatic β Cells in Medaka.
Takayoshi Otsuka,Hiroyuki Takeda +1 more
TL;DR: Transgenic lines are generated, in which β cells can be specifically ablated using the nitroreductase (NTR)/metronidazole (Mtz) system, and it is found that medaka rapidly regenerate β cells.
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