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Cyclins D2 and D1 Are Essential for Postnatal Pancreatic β-Cell Growth

机译：细胞周期蛋白D2和D1对出生后胰腺β细胞的生长至关重要

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Regulation of adult β-cell mass in pancreatic islets is essential to preserve sufficient insulin secretion in order to appropriately regulate glucose homeostasis. In many tissues mitogens influence development by stimulating D-type cyclins (D1, D2, or D3) and activating cyclin-dependent kinases (CDK4 or CDK6), which results in progression through the G1 phase of the cell cycle. Here we show that cyclins D2 and D1 are essential for normal postnatal islet growth. In adult murine islets basal cyclin D2 mRNA expression was easily detected, while cyclin D1 was expressed at lower levels and cyclin D3 was nearly undetectable. Prenatal islet development occurred normally in cyclin D2?/? or cyclin D1+/? D2?/? mice. However, β-cell proliferation, adult mass, and glucose tolerance were decreased in adult cyclin D2?/? mice, causing glucose intolerance that progressed to diabetes by 12 months of age. Although cyclin D1+/? mice never developed diabetes, life-threatening diabetes developed in 3-month-old cyclin D1?/+ D2?/? mice as β-cell mass decreased after birth. Thus, cyclins D2 and D1 were essential for β-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in β cells could prevent or cure diabetes.
机译：调节胰岛中成年β细胞的质量对于保持足够的胰岛素分泌至关重要，以便适当调节葡萄糖的体内稳态。在许多组织中，促细胞分裂剂通过刺激D型细胞周期蛋白（D1，D2或D3）并激活细胞周期蛋白依赖性激酶（CDK4或CDK6）来影响发育，从而导致其通过G 1 期的进程细胞周期。在这里，我们显示细胞周期蛋白D2和D1对于正常的产后胰岛生长至关重要。在成年鼠胰岛中，很容易检测到基础细胞周期蛋白D2 mRNA的表达，而细胞周期蛋白D1的表达水平较低，而细胞周期蛋白D3则几乎无法检测到。产前胰岛发育正常发生在 cyclin D2 ？ / ？或 cyclin D1 < sup> + / ？ D2 ？ / ？鼠标。但是，成年 cyclin D2 ？ / ？的β细胞增殖，成年质量和葡萄糖耐量降低。小鼠，导致葡萄糖耐受不良，并在12个月大时发展为糖尿病。尽管 cyclin D1 + / ？小鼠从未患上糖尿病，但威胁生命的糖尿病却发生在3个月大的 cyclin D1 ？ / + D2 ？ / ？小鼠出生后β细胞质量下降。因此，细胞周期蛋白D2和D1对于成年小鼠的β细胞扩增至关重要。严格控制β细胞中D型细胞周期蛋白活性的策略可以预防或治愈糖尿病。

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