β-Cell dysfunction in diabetes: a crisis of identity?
Type 2 diabetes is characterized by insulin resistance and a progressive loss of β-cell function induced by a combination of both β-cell loss and impaired insulin secretion from remaining β-cells. Here, we review the fate of the β-cell under chronic hyperglycaemic conditions with regard to β-cell mass, gene expression, hormone content, secretory capacity and the ability to de- or transdifferentiate into other cell types. We compare data from various in vivo and in vitro models of diabetes with a novel mouse model of inducible, reversible hyperglycaemia (βV59M mice). We suggest that insulin staining using standard histological methods may not always provide an accurate estimation of β-cell mass or number. We consider how β-cell identity is best defined, and whether expression of transcription factors normally found in islet progenitor cells, or in α-cells, implies that mature β-cells have undergone dedifferentiation or transdifferentiation. We propose that even in long-standing diabetes, β-cells predominantly remain β-cells-but not as we know them.
Department of Physiology, Anatomy and Genetics and OXION, University of Oxford, Oxford, UK.
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Brereton
Department of Physiology, Anatomy and Genetics and OXION, University of Oxford, Oxford, UK.
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Rohm
Department of Physiology, Anatomy and Genetics and OXION, University of Oxford, Oxford, UK. frances.ashcroft@dpag.ox.ac.uk.
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FM
Ashcroft
D000818:Animals; D054337:Cell Dedifferentiation; D054338:Cell Transdifferentiation; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000166:cytology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000166:cytology
D007328:Insulin
dedifferentiation; diabetes; insulin content; transdifferentiation; β-cell