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首页> 外文期刊>Cell cycle >Cyclin D2 is sufficient to drive beta cell self-renewal and regeneration
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Cyclin D2 is sufficient to drive beta cell self-renewal and regeneration

机译：细胞周期蛋白D2足以驱动β细胞自我更新和再生

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摘要

Diabetes results from an inadequate mass of functional beta cells, due to either beta cell loss caused by autoimmune destruction (type I diabetes) or beta cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate beta cell mass may be key to developing new techniques that foster beta cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal beta cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive beta cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in beta cells, we show that cyclin D2 overexpression increases beta cell self-renewal post-weaning and results in increased beta cell mass. beta cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. beta cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive beta cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in beta cells of cyclin D2(-/-) mice. Transgenic overexpression of cyclin D2 in cyclin D2(-/-) beta cells was sufficient to restore beta cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2(-/-) littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate beta cell self-renewal and that manipulation of its expression could be used to enhance beta cell regeneration.
机译：糖尿病因功能性β细胞质量不足，由于由自身免疫性破坏（I型糖尿病）或β细胞失效响应胰岛素抵抗（II型糖尿病）引起的β细胞损失。阐明调节β细胞质量的机制可以是开发培养诱使β细胞再生作为治疗糖尿病的细胞疗法的新技术的关键。虽然先前的研究得出结论，但是，如果小鼠中的产后β细胞自我更新需要细胞周期蛋白D2，则在短周期蛋白D2足以驱动β细胞自我更新时尚不清楚。使用特定于β细胞的转基因小鼠特异性的细胞周期蛋白D2，我们表明细胞周期蛋白D2过表达增加了β细胞自我更新后断奶和导致β细胞质量增加。过表达Cyclin D2的β细胞响应于葡萄糖刺激，表明它们在功能上是成熟的。过度表达细胞周期蛋白D2的β细胞在链脲佐菌素毒性诱导后表现出增强的再生能力。为了了解Cyclin D2过表达足以驱动β细胞自我更新，我们产生了一种新的小鼠模型，其中Cyclin D2仅在细胞周期蛋白D2（ - / - ）小鼠的β细胞中。细胞周期蛋白D2（ - / - ）β细胞中细胞周期蛋白D2的转基因过表达足以恢复β细胞质量，保持正常性血糖，并与细胞周期蛋白D2（ - / - ）窝相比，提高再生能力。我们的结果表明，细胞周期蛋白D2足以调节β细胞自我更新，并且可以使用其表达的操纵来增强β细胞再生。

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