title: β-cell dedifferentiation in diabetes is important, but what is it?
abstract: This commentary discusses the concept of β-cell dedifferentiation in diabetes, which is important but not well defined. A broad interpretation is that a state of differentiation has been lost, which means changes in gene expression as well as in structural and functional elements. Thus, a fully mature healthy β cell will have its unique differentiation characteristics, but maturing cells and old β cells will have different patterns of gene expression and might therefore be considered as dedifferentiated. The meaning of dedifferentiation is now being debated because β cells in the diabetic state lose components of their differentiated state, which results in severe dysfunction of insulin secretion. The major cause of this change is thought to be glucose toxicity (glucotoxicity) and that lowering glucose levels with treatment results in some restoration of function. An issue to be discussed is whether dedifferentiated β cells return to a multipotent precursor cell phenotype or whether they follow a different pathway of dedifferentiation.
authors.affiliation: Section on Islet Cell and Regenerative Biology; Research Division; Joslin Diabetes Center; Harvard Medical School; Boston, MA USA.
authors.forename: Gordon C
authors.initials: GC
authors.lastname: Weir
authors.affiliation: Section on Islet Cell and Regenerative Biology; Research Division; Joslin Diabetes Center; Harvard Medical School; Boston, MA USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Aguayo-Mazzucato
authors.affiliation: Section on Islet Cell and Regenerative Biology; Research Division; Joslin Diabetes Center; Harvard Medical School; Boston, MA USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Bonner-Weir
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D005947:Glucose / Q000633:toxicity*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D039902:Multipotent Stem Cells
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; D005947:Glucose
keywords: dedifferentiation; diabetes; differentiation; insulin secretion; islets; β cell