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Pancreatic islets

内分泌

关键词内分泌 临床研究术语 细胞

词汇介绍

拓展阅读

解析

pancreatic 英 /ˌpæŋkriˈætɪk/  美 /ˌpæŋkriˈætɪk/

释    义   adj. 胰的;胰腺的

例    句   Jobs was diagnosed with a rare form of pancreatic cancer in 2003, though he put off treatment until mid-2004.乔布斯在2003年被诊断出患了一种罕见的胰腺癌,虽然他一直将治疗推迟到2004年中。

 

islets  

释    义   n. 小岛(islet的复数)

例    句   The team noticed that in the daughters of fat fathers, these islets had shrunk, compared with those of the control daughters.莫里斯的团队注意到,和对照组的雌鼠相比,父亲肥胖的雌鼠身上发生了胰岛萎缩。

概述

概述


胰岛是胰腺各区具有内分泌功能(激素产生)的细胞,在1869年德国病理解剖学家保罗朗格汉斯发现的。胰岛占胰脏体积的1%2%,并接受胰岛10-15%的血流。胰岛以密度途径排列在整个人类胰腺中,在葡萄糖的代谢中很重要。


结构


大约有300万个胰岛以密度路线的形式分布在健康成年人的胰腺中,每个胰岛的直径平均约为0.1毫米(109微米)。每一个都通过一个薄的纤维结缔组织囊与周围的胰腺组织分开,该囊与整个胰腺其余部分交织的纤维结缔组织是连续的。


功能


葡萄糖/胰岛素:激活β细胞并抑制α细胞;糖原/胰高血糖素:激活α细胞,从而激活β细胞和δ细胞;生长抑素:抑制α细胞和β细胞。


大量G蛋白偶联受体(GPCR)调节胰岛中胰岛素,胰高血糖素和生长抑素的分泌,其中一些GPCR是用于治疗2型糖尿病的药物的靶标(ref GLP-1受体激动剂,DPPIV抑制剂)。


临床意义


糖尿病胰岛的β细胞分泌胰岛素,因此在糖尿病中起重要作用。据认为,它们被免疫攻击破坏了。但是,也有迹象表明β细胞没有被破坏,只是变得无功能。


移植由于在1型糖尿病中胰腺胰岛中的β细胞通过自身免疫过程被选择性破坏,因此临床医生和研究人员正在积极地进行胰岛移植,以恢复生理性β细胞功能,这将为完整的胰腺移植或人工胰岛提供替代方法胰腺。

A Peninsular Structure Coordinates Asynchronous Differentiation with Morphogenesis to Generate Pancreatic Islets复制标题

一个半岛结构协调异步分化与形态发生生成胰岛。

发表时间:2019-02-07

影响指数:36.2

作者: Nadav Sharon

期刊:cell

Type 1 diabetes (T1D) is caused by the destruction of insulin-producing b cells. These cells reside within the pancreatic islets of Langerhans, which also contain glucagon-generating a cells and small numbers of d, ε, and PP cells that produce the hormones somatostatin, ghrelin, and pancreatic polypeptide, respectively. Islet transplantation from cadavers has proved highly effective in alleviating T1D, but donor scarcity makes in vitro-generated islets an attractive substitute. Recent success with in vitro generation of insulin-producing b cells and a few other endocrine cell types from human pluripotent cells lends hope to establishing such an alternative source. However, increasing evidence indicates that proper glucose regulation requires coordination between the various islet cell types, and the islet’s internal arrangement supports that requirement. It may therefore be advantageous to produce whole islets in vitro rather than differentiating cells into a specific cell type. However, this requires recapitulating tissue morphogenesis in addition to cell differentiation. In mice, endocrine progenitors appear around E12.5, and their production rate peaks around E15.5, concurrent with an overall expansion of the primordial pancreas termed ‘‘the secondary transition’’. The endocrine progenitors emerge from a network of epithelial tubules, or ‘‘cords,’’ found in the core of the developing pancreas. New progenitors form in a continuous flux and differentiate toward their specific fate in an asynchronous manner. As cells differentiate, they are thought to undergo epithelial-to-mesenchymal transition (EMT), which renders them motile and allows them to migrate away from the cords, dispersing into the surrounding mesenchyme. Once they have acquired their particular fate and activated their specific hormones, the cells are believed to aggregate into small clusters that later constitute the complete islet. This dispersal-aggregation model describes how islets form and assemble away from the pancreatic ducts, which are likewise descendants of the epithelial cords. However, the model fails to explain how the differentiated endocrine cells find one another and assemble in the surrounding mesenchyme. Equally important, it does not explain how the islet acquires its final unique architecture. Mature islets in mice are built as an internal core of b cells surrounded by a mantle of a cells. In humans, this core-mantle architecture is maintained in small islets, whereas larger islets are built as composites of small core-mantle components.

译文

1型糖尿病(T1D)是由破坏胰岛素的b细胞引起的。这些细胞位于朗格汉斯的胰岛中,该胰岛也含有胰高血糖素生成细胞和少量分别产生生长激素抑制素,生长素释放肽和胰腺多肽激素的d,ε和PP细胞。尸体的胰岛移植已被证明在减轻T1D方面非常有效,但是供体的缺乏使体外产生的胰岛成为有吸引力的替代品。从人多能细胞中体外产生胰岛素生产性b细胞和其他一些内分泌细胞类型的最新成功,为建立这种替代来源提供了希望。但是,越来越多的证据表明,适当的葡萄糖调节需要在各种胰岛细胞类型之间进行协调,并且胰岛的内部结构支持该要求。因此,在体外产生完整的胰岛而不是将细胞分化为特定的细胞类型可能是有利的。然而,除了细胞分化之外,这还需要概括组织形态发生。在小鼠中,内分泌祖细胞出现在E12.5左右,它们的生产率峰值在E15.5左右,同时原始胰脏的整体扩张也被称为“第二代过渡”。内分泌祖细胞来自于发育中的胰腺核心的上皮小管网络或“绳索”。新的祖先不断地形成,并以异步的方式向着自己的命运分化。随着细胞的分化,它们被认为经历了上皮-间充质转化(EMT),这使它们运动,并使它们从脐带移走,分散到周围的间充质中。一旦它们获得了特定的命运并激活了它们的特定激素,就认为细胞会聚集成小簇,这些簇随后构成完整的胰岛。该扩散-聚集模型描述了胰岛如何形成以及如何从胰管形成和聚集,胰管同样是上皮索的后代。但是,该模型无法解释分化的内分泌细胞如何相互发现并在周围的间充质中组装。同样重要的是,它没有解释胰岛如何获得其最终的独特架构。小鼠中成熟的胰岛被构建为b细胞的内部核心,被细胞的外罩包围。在人类中,这种核-幔结构被保存在小的胰岛中,而较大的胰岛则是由小的核-幔组分组成的复合体。

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