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
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Patent
Methods for inducing insulin production and uses thereof
TL;DR: In this article, the authors proposed methods of inducing insulin production in delta-cells and converting delta cells into insulin producing cells, as well as methods of preventing and/or treating diabetes and agents and compositions useful in said methods.
Journal ArticleDOI
Effects of genetics and in utero diet on murine pancreatic development.
Chia-Lei Lin,Lyda Williams,Yoshinori Seki,Harpreet Kaur,Kirsten Hartil,Ariana Fiallo,A. Scott Glenn,Ellen B. Katz,Maureen J. Charron,Patricia Vuguin +9 more
TL;DR: In contrast to WT HFD pancreata, HFD exposure did not alter pancreatic islet morphology in fetuses with GLUT4 haploinsufficiency; this may be mediated in part by increased Igf2 expression.
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Harnessing the Pancreatic Stem Cell
TL;DR: Alternative strategies and potential sources of pancreatic stem cells are considered and the possibility of overcoming restrictions on tissue supply associated with transplantation of donor islets is considered.
Book ChapterDOI
The Basic Principles of Stem Cells
Jaroslav Mokry,Rishikaysh Pisal +1 more
TL;DR: Some properties of stem cells are so characteristic that they are used in functional assays as a proof of true stem cells; most in vitro methods are based on clonogenic assays, while in vivo tests rely on serial transplantation to demonstrate the long-term maintenance of self-renewal capacity.
Journal ArticleDOI
Beta-cell function and human islet transplantation: can we improve?
Jennifer Chen,Jenny E. Gunton +1 more
TL;DR: Islet transplantation, a therapeutic option to treat type 1 diabetes, is not yet as successful as whole-pancreas transplantation as a treatment for diabetes as mentioned in this paper.
References
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Book
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Shankar Srinivas,Tomoko Watanabe,Chyuan-Sheng Lin,Chris M William,Yasuto Tanabe,Thomas M. Jessell,Frank Costantini +6 more
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Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation.
TL;DR: This work introduces a method for genetic lineage tracing to determine the contribution of stem cells to a tissue of interest and suggests that terminally differentiated β-cells retain a significant proliferative capacity in vivo and casts doubt on the idea that adult stem cells have a significant role in β-cell replenishment.
Journal ArticleDOI
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.
TL;DR: This study identifies a specific combination of three transcription factors (Ngn3) Pdx1 and Mafa that reprograms differentiated pancreatic exocrine cells in adult mice into cells that closely resemble β-cells, and suggests a general paradigm for directing cell reprogramming without reversion to a pluripotent stem cell state.
Journal ArticleDOI
Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats.
TL;DR: It is reported that exendin-4, a long-acting GLP-I agonist, stimulates both the differentiation of beta-cells from ductal progenitor cells (neogenesis) and proliferation of Beta-cells when administered to rats and holds promise as a novel therapy to stimulate beta-cell growth and differentiation when administer to diabetic individuals with reduced beta- cell mass.
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