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法国会不会走在前面,听说开始人体实验了

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  • TA的每日心情
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    2018-7-21 07:38
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    [LV.3]家园青年

    发表于 2018-1-11 09:41:35 | 显示全部楼层 |阅读模式
    Inserm researchers led by Patrick Collombat at Unit 1091,“Institute of Biology Valrose” (Inserm/CNRS/Nice Sophia Antipolis University), show that GABA, a neurotransmitter that is sometimes used as a dietary supplement, can induce the regeneration of insulin-producing cells. This discovery, confirmed in mice and partially validated in humans, gives new hope to patients with type 1 diabetes.

    This research is published in the journal Cell.

    Type 1 diabetes is a disease characterised by the selective loss of cells that produce insulin, a hormone that lowers blood sugar levels upon sugar intake. These cells are called pancreatic beta cells. Discovering how to regenerate these cells is a major research challenge, as current treatments are not always sufficient in preventing (serious) complications.

    Scientists have shown in previous studies that it is possible to regenerate pancreatic beta cells by genetically transforming cells that resemble them: the glucagon-secreting alpha cells. This approach involved the forced activation of the Pax4 gene in all alpha cells. The results also proved that these alpha cells were continuously regenerated and again converted into beta cells, leading to a massive increase in the number of beta cells. “This advance is significant, but it is not possible to carry out this approach in humans,” explains Patrick Collombat, Inserm Research Director. To eventually translate their findings to human, the scientists therefore initiated a search for compounds mimicking the effects of the Pax4 gene.

    In this new study, the research team demonstrates that this effect can be induced with no genetic modification using GABA, a neurotransmitter that is naturally present in the body and also available as a dietary supplement.

    In mice, GABA induces the continuous, yet controlled, regeneration of pancreatic alpha cells and their transformation into insulin-producing beta cells. The regenerated cells are functional and can cure chemically-induced diabetes multiple times.

    With regards to humans, researchers observe that in pancreatic islets (which contain both alpha- and beta-cells) treated with GABA, the number of glucagon-producing alpha-cells is decreased by 37% while a 24% increase in insulin-producing cell count is noted, suggestive of a conversion of alpha-cells into beta-cells.

    Finally, by transplanting the equivalent of 500 human islets to mice, the same results are obtained after supplementing the animals for 1 month with GABA (daily). These results are truly encouraging for a putative application in humans. Accordingly, a pilot clinical trial will soon be initiated to determine whether GABA may effectively help patients with type 1 diabetes.

    These studies received financial support from ERC and the Juvenile Diabetes Research Foundation.

    Inserm 的研究人员由帕特里克 Collombat 在1091单元, 生物 Valrose 研究所 (Inserm/CNRS/尼斯索菲亚安蒂波利斯大学), 表明, GABA, 一种神经递质, 有时被用作膳食补充剂, 可以诱导再生胰岛素生成细胞。这一发现, 证实在小鼠和部分验证的人, 给病人新的希望1型糖尿病。 这项研究发表在期刊单元。 1型糖尿病是一种疾病, 其特征是选择性地丧失产生胰岛素的细胞, 这种激素在糖摄入时降低血糖水平。这些细胞被称为胰β细胞。发现如何再生这些细胞是一个主要的研究挑战, 因为目前的治疗并不总是足够的预防 (严重) 并发症。 科学家在先前的研究中已经表明, 通过基因转化的细胞 (类似于胰高血糖素分泌的α细胞) 可以再生胰腺β细胞。这种方法涉及在所有α细胞中强制激活 Pax4 基因。结果还证明, 这些α细胞不断再生, 并再次转化为β细胞, 导致β细胞数量的大量增加。Inserm 研究总监帕特里克 Collombat 解释道: 这一进步是重要的, 但在人类中不可能实现这种方法。为了最终将他们的发现转化为人类, 科学家们开始寻找模仿 Pax4 基因的作用的化合物。 在这项新的研究中, 研究小组表明, 这种效应可以诱导没有基因修饰使用 GABA, 一种神经递质, 自然存在于体内, 也可作为膳食补充剂。 在小鼠中, GABA 诱导连续, 但控制, 胰腺α细胞的再生和转化为胰岛素产生的β细胞。再生细胞具有功能性, 可多次治疗化学诱导的糖尿病。 关于人类, 研究人员观察到, 在胰岛 (其中含有α和β细胞) 治疗的 GABA, 胰高血糖素产生的α细胞的数量减少了 37, 而24 增加的胰岛素产生细胞计数被指出,暗示将α细胞转化为β细胞。 最后, 通过将相当于500人的胰岛移植到小鼠身上, 在用 GABA (每日) 补充动物1月后得到同样的结果。这些结果对于人类的一个假定的应用是真正鼓舞人心的。因此, 不久将开始一项试验性临床试验, 以确定 GABA 是否能有效地帮助1型糖尿病患者。 这些研究得到了紧急救济和青少年糖尿病研究基金会的资助。
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    Diabetes Genetics

    Our group is involved in understanding the molecular mechanisms underlying Diabetes. Both Type I Diabetes (insulinodependent) and Type II (non insulinodependent) diabetes ultimately result in the selective loss of insulin-producing beta-cells in the endocrine pancreas (Figure 1). The subsequent lack in insulin hormone induces a blood hyperglycemia that may be attenuated by daily injection of exogenous insulin hormone. Nevertheless, due to variations in glycemia, vascular damages, blindness, amputation or even death may occur.


    Figure 1: Type I diabetes in mouse and human

    Aiming to overcome these complications, the in vitro generation of pancreatic beta cells from stem or progenitor cells appears as a promising alternative. However, to design rational protocols that will allow the differentiation of beta cells, it is imperative to uncover the molecular determinant controlling their genesis.

    Using the Mouse to study diabetes
    We belong to a NIH-funded consortium whose goal is to gain further insight into the mechanisms regulating the genesis of the mouse pancreas and apply this knowledge to improve the treatment of diabetes in human. Toward this aim, we have identified two transcription factors, Arx and Pax4, playing a crucial role in the genesis of the different endocrine cell subtypes, including insulin-secreting beta-cells. Specifically, we demonstrated that Arx controls the development of alpha- and PP-cells, whereas Pax4 regulates the genesis of beta- and delta-cell (Animated Figure 2). Importantly, our latest results indicate that these factors are sufficient to literally transform adult alpha-cells into beta-cells and vice versa.


    Figure 2: Diaporama auto-animé représentant les modifications du pancréas endocrine observées dans les animaux transgéniques pour Arx ou Pax4.

    Generating beta-cells from other pancreatic cells
    Building upon these findings, we recently discovered that duct cells can also be transformed into beta cells in vivo and that such cells can cure diabetes in mice. To further understand the genetic determinants implicated in these multiple conversions, we use transcriptome analysis, gain- and loss-of-function approaches and small molecule screens. This work is funded by Juvenile Diabetes research foundation and is performed in tight collaboration with the pharmaceutical company Novonordisk (Copenhagen-Denmark) and the Broad Institute of Harward and MIT (Boston-USA).

    HOMEINSTITUTE 研究团队新闻与活动议程联系糖尿病遗传学我们的小组参与了了解糖尿病的分子机制。I 型糖尿病 (insulinodependent) 和 II 型 (非 insulinodependent) 型糖尿病最终导致选择性丧失胰岛素产生的β细胞在内分泌胰腺 (图 1)。随后胰岛素激素的缺乏导致血液高血糖, 可能通过每日注射外源性胰岛素激素而减弱。然而, 由于血糖的变化, 血管损伤, 失明, 截肢甚至死亡可能发生。 图 1: I 型糖尿病在小鼠和人类的目的, 以克服这些并发症, 从茎或祖细胞的胰腺β细胞的体外生成出现作为一个有前途的选择。然而, 要设计出能够允许β细胞分化的合理的协议, 就必须揭开控制其成因的分子行列式。 使用鼠标来研究糖尿病我们属于一个 NIH 资助的联合体, 其目的是进一步了解调节小鼠胰腺起源的机制, 并应用这些知识来改善人类糖尿病的治疗。为了达到这个目的, 我们确定了两个转录因子, Arx 和 Pax4, 在不同的内分泌细胞亚型, 包括胰岛素分泌的β细胞的起源中扮演了关键的角色。具体来说, 我们证明 Arx 控制着α和 PP 细胞的发育, 而 Pax4 调节β和三角洲细胞的起源 (动画图 2)。重要的是, 我们的最新结果表明, 这些因素足以将成人α细胞转化为β细胞, 反之亦然。 图 2: Diaporama auto-animé représentant 的修改 pancréas 内分泌 observées dan les animaux transgéniques 倒 Arx 瓯 Pax4. 从其他胰腺细胞生成β细胞根据这些发现, 我们最近发现, 导管细胞也可以在体内转化为β细胞, 这样的细胞可以治疗小鼠的糖尿病。为了进一步了解这些多重转换所牵连的遗传决定因素, 我们使用转录分析、增益和功能方法和小分子筛。这项工作由青少年糖尿病研究基金会资助, 并与制药公司 Novonordisk (哥本哈根-丹麦) 和哈佛和麻省理工学院 (波士顿-美国) 的广泛研究所进行紧密合作。

  • TA的每日心情
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    2018-6-6 01:13
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    [LV.6]家园支柱

    发表于 2018-1-11 15:17:27 | 显示全部楼层
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    发表于 2018-1-11 20:53:22 | 显示全部楼层
    科学无国界,造福人类就好。
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