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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Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via Pdx1 Silencing.
Hugo Bernard,Ana Teijeiro,Almudena Chaves-Pérez,Cristian Perna,Basanthi Satish,Anna Novials,Jennifer P. Wang,Nabil Djouder +7 more
TL;DR: URI and DNMT1 expression and PDX1 silencing provide a causal link between enterovirus infection and diabetes.
Journal ArticleDOI
Insulin therapy improves islet functions by restoring pancreatic vasculature in high-fat diet-fed streptozotocin-diabetic rats.
TL;DR: In this paper, the pancreatic microvasculature was analyzed in diabetic rats after insulin treatment and the results suggest that insulin treatment improves islet recovery by increasing angiogenesis in the pancreas.
Journal ArticleDOI
Mild hyperglycemia triggered islet function recovery in streptozotocin-induced insulin-deficient diabetic rats.
TL;DR: The effect of moderately elevated glucose on β‐cell mass expansion and islet function recovery in diabetic animal models is tested to effectively promote β‐ cell replication in various models in vitro and in normal rodents.
Journal ArticleDOI
FCoR-Foxo1 Axis Regulates α-Cell Mass through Repression of Arx Expression
TL;DR: It is demonstrated that Fcor-knockout mice (FcorKO) exhibit significantly increased α- cell mass, expression of the master α-cell regulatory transcription factor Aristaless-related homeobox (Arx), which can be normalized by β-cell-specific FCoR overexpression (FCorKO-βFcor), and exhibit β-to-α-cell conversion.
Journal ArticleDOI
The CD34 surface antigen is restricted to glucagon-expressing cells in the early developing bovine pancreas.
Claudia Merkwitz,Tiina Pessa-Morikawa,Paul Lochhead,Gessner Reinhard,Michiharu Sakurai,Antti Iivanainen,Albert M. Ricken +6 more
TL;DR: It is demonstrated that CD34 and/or CD133-reactive cells contribute to the pancreatic alpha cell population during early foetal development in cattle.
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