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
More filters
Journal ArticleDOI
Stochastic State Transitions Give Rise to Phenotypic Equilibrium in Populations of Cancer Cells
Piyush Gupta,Christine M. Fillmore,Guozhi Jiang,Sagi Shapira,Kai Tao,Charlotte Kuperwasser,Charlotte Kuperwasser,Eric S. Lander,Eric S. Lander,Eric S. Lander +9 more
TL;DR: It is shown that subpopulations of cells purified for a given phenotypic state return towards equilibrium proportions over time, and this findings contribute to the understanding of cancer heterogeneity and reveal how stochasticity in single-cell behaviors promotes phenotypesic equilibrium in populations of cancer cells.
Journal ArticleDOI
Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure
TL;DR: It is proposed that dedifferentiation trumps endocrine cell death in the natural history of β cell failure and suggested that treatment ofβ cell dysfunction should restore differentiation, rather than promoting β cell replication.
Journal ArticleDOI
The repair Schwann cell and its function in regenerating nerves
Kristjan R. Jessen,Rhona Mirsky +1 more
TL;DR: The transcription factor c‐Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non‐myelin (Remak) Schwann cells to repair cells after injury.
Journal ArticleDOI
Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes
TL;DR: Evidence that genetic and environmental factors can lead to hyperglycemia, dyslipidemia, inflammation, and autoimmunity, resulting in β-cell dysfunction, thereby triggering the pathogenesis of diabetes is presented.
Journal ArticleDOI
Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration.
TL;DR: Current research aims to understand how the processes of dedifferentiation, transdifferentiation or reprogramming work and to eventually harness them for use in regenerative medicine.
References
More filters
Journal ArticleDOI
Differences in Glucose Transporter Gene Expression between Rat Pancreatic α- and β-Cells Are Correlated to Differences in Glucose Transport but Not in Glucose Utilization
TL;DR: Differences in glucose transporter gene expression between α- and β-cells can be correlated with differences in glucose transport kinetics but not with different glucose utilization rates.
Journal ArticleDOI
Pancreatic neurogenin 3-expressing cells are unipotent islet precursors
TL;DR: A model whereby Ngn3+ cells are monotypic (i.e. unipotent) precursors is proposed, and this paradigm is used to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans.
Journal ArticleDOI
Ablation of islet endocrine cells by targeted expression of hormone-promoter-driven toxigenes
Pedro Luis Herrera,Joaquin Huarte,Romain Zufferey,Anthony Nichols,Bernadette Mermillod,Jacques Philippe,Pedro Muniesa,Francesca Sanvito,Lelio Orci,Jean-Dominique Vassalli +9 more
TL;DR: It is suggested that pancreatic polypeptide gene-expressing cells are indispensable for the differentiation of islet beta and delta cells because the former produce a necessary paracrine or endocrine factor and/or operate through a cell-lineage relationship.
Journal ArticleDOI
The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.
Harry Heimberg,A. De Vos,Karen Moens,E. Quartier,Luc Bouwens,Daniel Pipeleers,E Van Schaftingen,Ole D. Madsen,Frans Schuit +8 more
TL;DR: The data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and mediate a mechanism for direct regulation of glucagon release by extracellular glucose and suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinases.
Journal ArticleDOI
Ontogeny of regeneration of β-cells in the neonatal rat after treatment with streptozotocin
TL;DR: The model shows that the pancreas of the young rat can rapidly regenerate a loss of beta-cells, and this is associated with hyperplasia of alpha-cells with an altered phenotype of increased GLP-1 synthesis.
Related Papers (5)
Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas.
Xiaobo Xu,Joke D'Hoker,Joke D'Hoker,Geert Stange,Geert Stange,Stefan Bonné,Stefan Bonné,Nico De Leu,Nico De Leu,Xiangwei Xiao,Xiangwei Xiao,Mark Van de Casteele,Mark Van de Casteele,Georg Mellitzer,Georg Mellitzer,Zhidong Ling,Zhidong Ling,Daniel Pipeleers,Daniel Pipeleers,Luc Bouwens,Luc Bouwens,Raphael Scharfmann,Raphael Scharfmann,Raphael Scharfmann,Gerard Gradwohl,Gerard Gradwohl,Gerard Gradwohl,Harry Heimberg,Harry Heimberg,Harry Heimberg +29 more