Stress-induced adaptive islet cell identity changes.
The different forms of diabetes mellitus differ in their pathogenesis but, ultimately, they are all characterized by progressive islet β-cell loss. Restoring the β-cell mass is therefore a major goal for future therapeutic approaches. The number of β-cells found at birth is determined by proliferation and differentiation of pancreatic progenitor cells, and it has been considered to remain mostly unchanged throughout adult life. Recent studies in mice have revealed an unexpected plasticity in islet endocrine cells in response to stress; under certain conditions, islet non-β-cells have the potential to reprogram into insulin producers, thus contributing to restore the β-cell mass. Here, we discuss the latest findings on pancreas and islet cell plasticity upon physiological, pathological and experimental conditions of stress. Understanding the mechanisms involved in cell reprogramming in these models will allow the development of new strategies for the treatment of diabetes, by exploiting the intrinsic regeneration capacity of the pancreas.
Department of Genetic Medicine and Development, Faculty of Medicine, Institute of Genetics and Genomics in Geneva (iGE3), and Centre facultaire du diabète, University of Geneva, Geneva, Switzerland.
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Cigliola
Department of Genetic Medicine and Development, Faculty of Medicine, Institute of Genetics and Genomics in Geneva (iGE3), and Centre facultaire du diabète, University of Geneva, Geneva, Switzerland.
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Thorel
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway.
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Chera
Department of Genetic Medicine and Development, Faculty of Medicine, Institute of Genetics and Genomics in Geneva (iGE3), and Centre facultaire du diabète, University of Geneva, Geneva, Switzerland. Pedro.Herrera@unige.ch.
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Herrera
D000818:Animals; D000066670:Cell Plasticity; D065150:Cellular Reprogramming; D003920:Diabetes Mellitus; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology; D051379:Mice; D012038:Regeneration; D013234:Stem Cells; D013312:Stress, Physiological
D007328:Insulin
adaptive cell plasticity; cell conversion; cell dedifferentiation; cell fate change; cell identity; cell reprogramming; cell transdifferentiation; diabetes; diabetes treatment; islet; pancreas; transgenic