β cell replication is the primary mechanism for maintaining postnatal β cell mass
Senta Georgia, Anil Bhushan
Senta Georgia, Anil Bhushan
Published October 1, 2004
Citation Information: J Clin Invest. 2004;114(7):963-968. https://doi.org/10.1172/JCI22098.
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Article Metabolism

β cell replication is the primary mechanism for maintaining postnatal β cell mass

Abstract

The endocrine pancreas undergoes major remodeling during neonatal development when replication of differentiated β cells is the major mechanism by which β cell mass is regulated. The molecular mechanisms that govern the replication of terminally differentiated β cells are unclear. We show that during neonatal development, cyclin D2 expression in the endocrine pancreas coincides with the replication of endocrine cells and a massive increase in islet mass. Using cyclin D2–/– mice, we demonstrate that cyclin D2 is required for the replication of endocrine cells but is expendable for exocrine and ductal cell replication. As a result, 14-day-old cyclin D2–/– mice display dramatically smaller islets and a 4-fold reduction in β cell mass in comparison to their WT littermates. Consistent with these morphological findings, the cyclin D2–/– mice are glucose intolerant. These results suggest that cyclin D2 plays a key role in regulating the transition of β cells from quiescence to replication and may provide a target for the development of therapeutic strategies to induce expansion and/or regeneration of β cells.

Authors

Senta Georgia, Anil Bhushan

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β cell mass in WT and cyclin D2–/– mice during postnatal development. (A...
β cell mass in WT and cyclin D2–/– mice during postnatal development. (A) The β cell mass per pancreas was estimated as the product of the relative cross-sectional area of β cells (determined by quantification of the cross-sectional area occupied by β cells divided by the cross-sectional area of total tissue) and the weight of the pancreas. β cell mass was measured at a postnatal age as indicated. Data are mean values ± SEM of four mice per genotype. In WT mice, β cell mass measurement showed a 4-fold increase by P14. In contrast, cyclin D2–/– littermates did not show any significant increase in β cell mass in the same period. (B) Body weights of cyclin D2 litters were measured to correspond to the β cell mass measurements during the postnatal period. The cyclin D2–/– mice weights do not differ from their littermates. (C) The relative β cell mass is calculated as a ratio of the β cell mass to body weight. Data are mean values ± SEM of ten mice per genotype.