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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Cyclin D2 mutant mice have decreased plasma insulin levels and impaired ...
Cyclin D2 mutant mice have decreased plasma insulin levels and impaired glucose tolerance. (A) Plasma insulin levels in WT and cyclin D2–/– mice following overnight fasting and 30 minutes after glucose challenge (2 g/kg body weight). Results are expressed as mean values ± SEM of four WT and cyclin D2–/– mice. (B) Blood glucose levels were measured after 16-hour fasting (time 0) and after glucose injection (2 g/kg body weight) in 12-week-old WT and cyclin D2–/– mice. Results are expressed as mean values ± SEM of three WT and cyclin D2–/– mice.