Pancreatic cells can morph to make insulin

Diabetes is characterized by persistent high blood sugar levels that occur when pancreatic insulin-producing β-cells are destroyed or are no longer able to secrete insulin. But researchers have discovered that other pancreatic cells can come to the rescue when insulin-producing cells are destroyed. In a new study published in Nature Cell Biology, a group of researchers including Duke Regeneration Next Fellow Valentina Cigliola, Ph.D, have reported that certain pancreatic cell types, the α- and δ-cells, can change their identity and reprogram into insulin-producers to make up for the insulin deficit upon β-cell loss.

Mouse pancreatic islet in which alpha-cells have been labeled with a fluorescent tag (green). Some of them have started to produce insulin (red), and the morphed cells appear as yellow (green-and-red merge). Image courtesy V. Cigliola.

Cigliola, her mentor Pedro Herrera, Ph.D., and their colleagues at the University of Geneva report on the molecular mechanisms controlling how α-cells behave after β-cell loss. By genetically and pharmacologically altering these mechanisms, Cigliola and colleagues were able to significantly increase the number of α-cells that produce insulin. They also showed that this newfound insulin-producing capacity is reversible, with α-cells switching back to their original role when physiological conditions are restored.

This study challenges the current belief that mature cell types remain stable and cannot morph into other stem cells, and has implications not only for the treatment of diabetes, but for tissue regeneration in many other organs and disease conditions.

Citation:   Valentina Cigliola, Luiza Ghila, Fabrizio Thorel, Léon van Gurp, Delphine Baronnier, Daniel Oropeza, Simone Gupta, Takeshi Miyatsuka, Hideaki Kaneto, Mark A. Magnuson, Anna B. Osipovich, Maike Sander, Christopher E. V. Wright, Melissa K. Thomas, Kenichiro Furuyama, Simona Chera, Pedro L. Herrera. Pancreatic islet-autonomous insulin and smoothened-mediated signalling modulate identity changes of glucagon α-cells. Nature Cell Biology, 2018; 20 (11): 1267 DOI: 10.1038/s41556-018-0216-y


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