A δ-cell subpopulation with a pro-β-cell identity contributes to efficient age-independent recovery in a zebrafish model of diabetes

• DOI: 10.7554/elife.67576
• Publication Date: 2022-01-21T13:00:19Z
• Authors: Claudio Andrés Ca...; Laura Massoz; Marie A Dupont; David Bergemann; Jordane Bourdouxhe; Arnaud Lavergne; Estefania Tarifeñ...; Christian SM Helker; Didier YR Stainier; Bernard Peers; Marianne M Voz; Isabelle Manfroid
• Keywords: Male; 0301 basic medicine; insulin; Somatostatin-Secreting Cells; QH301-705.5; Science; somatostatin; Diabetes Mellitus, Experimental; 03 medical and health sciences; Insulin-Secreting Cells; Animals; Insulin; pancreas; Biology (General); Pancreas; Zebrafish; 0303 health sciences; diabetes; Q; R; Cell Biology; zebrafish; regeneration; Medicine; Female; Somatostatin

Restoring damaged β-cells in diabetic patients by harnessing the plasticity of other pancreatic cells raises the questions of the efficiency of the process and of the functionality of the new Insulin-expressing cells. To overcome the weak regenerative capacity of mammals, we used regeneration-prone zebrafish to study β-cells arising following destruction. We show that most new insulin cells differ from the original β-cells as they coexpress Somatostatin and Insulin. These bihormonal cells are abundant, functional and able to normalize glycemia. Their formation in response to β-cell destruction is fast, efficient, and age-independent. Bihormonal cells are transcriptionally close to a subset of δ-cells that we identified in control islets and that are characterized by the expression of somatostatin 1.1 (sst1.1) and by genes essential for glucose-induced Insulin secretion in β-cells such as pdx1, slc2a2 and gck. We observed in vivo the conversion of monohormonal sst1.1-expressing cells to sst1.1+ ins + bihormonal cells following β-cell destruction. Our findings support the conclusion that sst1.1 δ-cells possess a pro-β identity enabling them to contribute to the neogenesis of Insulin-producing cells during regeneration. This work unveils that abundant and functional bihormonal cells benefit to diabetes recovery in zebrafish.