β-Cell dysfunction in diabetes: a crisis of identity?

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2016-09, Vol.18 (S1), p.102-109
• Main Authors: Brereton, M. F., Rohm, M., Ashcroft, F. M.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Beta cells; Cell Dedifferentiation; Cell Transdifferentiation; dedifferentiation; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Gene expression; Glucagon-Secreting Cells - cytology; Humans; Hyperglycemia; Hyperglycemia - metabolism; In Vitro Techniques; Insulin; Insulin - metabolism; insulin content; Insulin resistance; Insulin Secretion; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Mice; Progenitor cells; Stem Cells - cytology; Transcription factors; transdifferentiation; β-cell
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12732

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.