Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro.
Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro.
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DOI：
10.3390/biom12020215
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发表时间：
2022-01-26
期刊：
影响因子：
5.5
通讯作者：
Georgia S
中科院分区：
文献类型：
--
作者：
Millette K;Rodriguez K;Sheng X;Finley SD;Georgia S
由于最近被诊断患有T1D的患者和患有T2D的患者具有残留的β细胞群，因此β细胞生物学中有相当大的努力来理解驱动β细胞再生的机制，作为用于扩大患者的残留β细胞群的潜在细胞疗法。小鼠和人类的研究都已经确定，β细胞群在怀孕期间迅速扩张。为了研究妊娠期间β细胞群扩增的机制，我们开发了一种新的体内和体外假孕模型。我们的模型表明，假孕促进β细胞群的扩大，在经产小鼠，这种扩大是由β细胞增殖，而不是肥大。重要的是，雌激素、孕激素和胎盘催乳素在假孕模型中诱导STAT5A信号传导，表明该模型成功地重现了妊娠诱导的β细胞复制。然后，我们建立了一个假孕激素的体外模型，发现雌激素和胎盘催乳素的组合诱导人胰岛和大鼠胰岛素瘤细胞中β细胞的复制。因此，与单独用雌二醇或胎盘催乳素处理的组相比，当经受假孕激素混合物时，体外和体内的β细胞均增加增殖。这里描述的假孕模型可能有助于为糖尿病患者诱导β细胞复制的新方法提供信息。
As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes.
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影响因子：
4.8
作者：
Mussmann, Rainer;Geese, Marcus;Austen, Matthias
通讯作者：
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影响因子：
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