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Physiol Rev. 2018 Jul 1;98(3):1143-1167. doi: 10.1152/physrev.00034.2016.

(Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives.

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Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Brussels , Belgium ; Diabetes Center, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, and Department of Medicine, University of California San Francisco , San Francisco, California ; Genentech Safety Assessment, South San Francisco, California ; Investigative Toxicology, UCB BioPharma, Braine-l'Alleud, Belgium ; Department of Pediatrics, Division of Pediatric Endocrinology, Ghent University, Hospital and Department of Pediatrics and Genetics , Ghent , Belgium ; Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels , Belgium ; and Department of Endocrinology, Algemeen Stedelijk Ziekenhuis Aalst, Aalst, Belgium.


Diabetes mellitus results from disturbed glucose homeostasis due to an absolute (type 1) or relative (type 2) deficiency of insulin, a peptide hormone almost exclusively produced by the beta cells of the endocrine pancreas in a tightly regulated manner. Current therapy only delays disease progression through insulin injection and/or oral medications that increase insulin secretion or sensitivity, decrease hepatic glucose production, or promote glucosuria. These drugs have turned diabetes into a chronic disease as they do not solve the underlying beta cell defects or entirely prevent the long-term complications of hyperglycemia. Beta cell replacement through islet transplantation is a more physiological therapeutic alternative but is severely hampered by donor shortage and immune rejection. A curative strategy should combine newer approaches to immunomodulation with beta cell replacement. Success of this approach depends on the development of practical methods for generating beta cells, either in vitro or in situ through beta cell replication or beta cell differentiation. This review provides an overview of human beta cell generation.

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