β cell replication is the primary mechanism for maintaining postnatal β cell mass
β cell replication is the primary mechanism for maintaining postnatal β cell mass
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DOI：
10.1172/jci200422098
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发表时间：
2004-10-01
影响因子：
15.9
通讯作者：
Bhushan, A
中科院分区：
文献类型：
--
作者：
Georgia, S;Bhushan, A
当分化的β细胞的复制是调节β细胞群的主要机制时，内分泌胰腺在新生儿发育期间经历主要重塑。控制终末分化β细胞复制的分子机制尚不清楚。我们发现，在新生儿的发展，细胞周期蛋白D2的表达在内分泌胰腺内分泌细胞的复制和胰岛质量的大量增加相一致。使用细胞周期蛋白D2（-/-）小鼠，我们证明，细胞周期蛋白D2是内分泌细胞的复制所需的，但外分泌和导管细胞复制是消耗品。结果，14日龄的细胞周期蛋白D2（-/-）小鼠与其WT同窝小鼠相比显示出显著更小的胰岛和4倍的β细胞质量减少。与这些形态学发现一致，细胞周期蛋白D2（-/-）小鼠是葡萄糖不耐受的。这些结果表明，细胞周期蛋白D2在调节β细胞从静止到复制的转变中发挥着关键作用，并且可能为开发诱导β细胞扩增和/或再生的治疗策略提供靶点。
The endocrine pancreas undergoes major remodeling during neonatal development when replication of differentiated beta cells is the major mechanism by which beta cell mass is regulated. The molecular mechanisms that govern the replication of terminally differentiated beta 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 beta 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 beta cells from quiescence to replication and may provide a target for the development of therapeutic strategies to induce expansion and/or regeneration of beta cells.