Abstract
Replication of β cells is an important source of β-cell expansion in early childhood. The recent linkage of type 2 diabetes with several transcription factors involved in cell cycle regulation implies that growth of the β-cell mass in early childhood might be an important determinant of risk for type 2 diabetes. Under some circumstances, including obesity and pregnancy, the β-cell mass is adaptively increased in adult humans. The mechanisms by which this adaptive growth occurs and the relative contributions of β-cell replication or of mechanisms independent of β-cell replication are unknown. Also, although there is interest in the potential for β-cell regeneration as a therapeutic approach in both type 1 and 2 diabetes, little is yet known about the potential sources of new β cells in adult humans. In common with other cell types, replicating β cells have an increased vulnerability to apoptosis, which is likely to limit the therapeutic value of inducing β-cell replication in the proapoptotic environment of type 1 and 2 diabetes unless applied in conjunction with a strategy to suppress increased apoptosis.
Key Points
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Replication of β-cells is important in growth of the β-cell mass during infancy in humans but is infrequent in adults, implying that most β cells are then quiescent
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The β-cell mass increases in response to obesity and pregnancy in humans, implying some ongoing capacity for β-cell turnover but much less than that in rodents
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The range of β-cell mass in nondiabetic humans far exceeds the adaptive increase in response to chronic insulin resistance, implying a wide range of growth in β-cell mass during infancy
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Sources of new β cells that do not rely on β-cell replication have been proposed but are as yet unproven in humans
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Newly forming β cells have an increased vulnerability to apoptosis, probably limiting potential β-cell regeneration
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Although β-cell regeneration has been proposed as a therapy for type 1 and type 2 diabetes, neither the extent that β-cell regeneration can be accomplished nor the mechanisms involved have been established in humans
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PC Butler has received investigator-initiated research grant funding from Merck, Novo Nordisk and Pfizer. The other authors declared no competing interests.
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Butler, P., Meier, J., Butler, A. et al. The replication of β cells in normal physiology, in disease and for therapy. Nat Rev Endocrinol 3, 758–768 (2007). https://doi.org/10.1038/ncpendmet0647
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DOI: https://doi.org/10.1038/ncpendmet0647
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