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Open AccessJournal ArticleDOI

Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss

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.

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Dedifferentiation, transdifferentiation and cell fusion: in vivo reprogramming strategies for regenerative medicine

TL;DR: The main mechanisms of tissue regeneration, underlying the importance of cell dedifferentiation and reprogramming are reviewed, with a particular focus on strategies aiming at the promotion of the body's self‐repairing mechanisms.
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Increased Frequency of Hormone Negative and Polyhormonal Endocrine Cells in Lean Individuals With Type 2 Diabetes

TL;DR: Degranulation and altered identity play at most a minor role in the beta cell deficit in lean T2D, and the increase in CPHN and polyhormonal cells precede diabetes onset is likely a response to stress rather than hyperglycemia, and may reflect attempted regeneration.
Journal ArticleDOI

Essential Roles for the Non-Canonical IκB Kinases in Linking Inflammation to Cancer, Obesity, and Diabetes

Chong Hyun Shin, +1 more
- 19 Feb 2019 - 
TL;DR: Current data on the functions and molecular mechanisms of TBK1 and IKKε in orchestrating inflammation to cancer, obesity, and diabetes are summarized.
Journal ArticleDOI

Targeted Mutation of NGN3 Gene Disrupts Pancreatic Endocrine Cell Development in Pigs.

TL;DR: The role of NEUROGENIN 3 (NGN3), a transcription factor involved in endocrine pancreas development has been investigated by CRISPR/Cas9 gene ablation and data support a critical role of NGN3 in porcine endocrine pancakes development.
Journal ArticleDOI

Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β-cell functions, and β-cell proliferation in male mice.

TL;DR: The results suggest that OSI-906 could exacerbate diabetes, especially in patients with insulin resistance, and suggest that the β-cell mass may expand in response to chemotherapy with this drug.
References
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Book

Manipulating the mouse embryo: A laboratory manual

TL;DR: Here are recorded the tech- niques for preparing, inserting and analysing DNA sequences, for retroviral infection of mice, for production and use of EC and EK cells as vehicles for engineered sequences and for nuclear transplantation - all against a background of the basic procedures required for pro- ducing and handling the em- bryos.
Journal ArticleDOI

Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus

TL;DR: In contrast to existing lacZ reporter lines, where lacZ expression cannot easily be detected in living tissue, the EYFP and ECFP reporter strains are useful for monitoring the expression of Cre and tracing the lineage of these cells and their descendants in cultured embryos or organs.
Journal ArticleDOI

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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