Conversion of Adult Pancreatic Alpha-cells to Beta-cells After Extreme Beta-cell Loss

Overview

Journal Nature

Specialty Science

Date 2010 Apr 6

PMID 20364121

Citations 602

Authors

Fabrizio Thorel

Virginie Nepote

Isabelle Avril

Kenji Kohno

Renaud Desgraz

Simona Chera

Pedro L Herrera

Affiliations

Soon will be listed here.

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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