Development and Regeneration in the Endocrine Pancreas

Figure 1

Regeneration routes in the adult endocrine pancreas. During normal development Pdx1-marked cells are fated to generate pancreas tissue. Subsequently, a small proportion of these cells labeled by the bHLH factor Ngn3 acquire endocrine cell destiny and give rise to hormone-producing cells, and consisting of beta-, alpha-, delta-, PP-, and epsilon-cells, producing insulin, glucagon, somatostatin, pancreatic polypeptide, and ghrelin, respectively. Following pancreatic injury different sources of stem/progenitor cell were proposed. It is well accepted that beta-cells are able to self-renew under physiological conditions or following pancreatic injury. However, other sources of beta-cell regeneration are under debate. In several animal models duct/duct-lining cells appear as the dominant source where stem/progenitor cells may reside. Interestingly, the forced expression of Pdx1, Ngn3, and MafA is able to allow transdifferentiation of acinar cells into insulin-producing cells in vivo [35]. Global ablation of beta-cells using diphtheria toxin led to some conversion of alpha- to beta-cells [20]. A more robust transdifferentiation of alpha- to beta-cells was observed following the combination of pancreatic duct ligation and alloxan-induced beta-cell injury [36, 37]. On the other hand, the misexpression of a single factor, Pax4 in alpha-cells, was able to endow these with functional beta-cell characteristic, and counter chemically induced diabetes in mice. This study clearly uncovered the robust-regenerative capacity of alpha-cells and provides a possible new source for generating beta-cells to develop revolutionary approaches to treat diabetes [32, 38, 39]. PDL: pancreatic duct ligation.