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胰岛素分泌和葡萄糖代谢增强的β细胞亚群在2型糖尿病中减少
2023-03-22 15:15

美国威尔康奈尔医学院James C. Lo研究组提出了胰岛素分泌和葡萄糖代谢增强的β细胞亚群在2型糖尿病中减少。2023年3月16日出版的《自然—细胞生物学》发表了这项成果。

他们使用单细胞转录组方法识别β细胞亚群。以CD63高表达为标志的β细胞的一个亚群富集了线粒体代谢基因的表达,与CD63lo β细胞相比表现出更高的线粒体呼吸。与来自CD63lo β细胞的伪胰岛相比,来自CD63hi β细胞的伪胰岛显示出葡萄糖刺激的胰岛素分泌增强。他们发现CD63hi β细胞在小鼠模型和2型糖尿病患者中减少。最后,将CD63hi而非CD63lo β细胞产生的伪胰岛移植到糖尿病小鼠中恢复葡萄糖稳态。

这些发现表明,失去特定的β细胞子集可能会导致糖尿病。重建或维持CD63hi β细胞的策略可能代表一种潜在的抗糖尿病治疗。

据悉,胰岛由分离的激素产生细胞组成,调节全身葡萄糖稳态。

附:英文原文

Title: A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes

Author: Rubio-Navarro, Alfonso, Gmez-Banoy, Nicols, Stoll, Lisa, Dndar, Friederike, Mawla, Alex M., Ma, Lunkun, Cortada, Eric, Zumbo, Paul, Li, Ang, Reiterer, Moritz, Montoya-Oviedo, Nathalia, Homan, Edwin A., Imai, Norihiro, Gilani, Ankit, Liu, Chengyang, Naji, Ali, Yang, Boris, Chong, Angie Chi Nok, Cohen, David E., Chen, Shuibing, Cao, Jingli, Pitt, Geoffrey S., Huising, Mark O., Betel, Doron, Lo, James C.

Issue&Volume: 2023-03-16

Abstract: The pancreatic islets are composed of discrete hormone-producing cells that orchestrate systemic glucose homeostasis. Here we identify subsets of beta cells using a single-cell transcriptomic approach. One subset of beta cells marked by high CD63 expression is enriched for the expression of mitochondrial metabolism genes and exhibits higher mitochondrial respiration compared with CD63lo beta cells. Human and murine pseudo-islets derived from CD63hi beta cells demonstrate enhanced glucose-stimulated insulin secretion compared with pseudo-islets from CD63lo beta cells. We show that CD63hi beta cells are diminished in mouse models of and in humans with type 2 diabetes. Finally, transplantation of pseudo-islets generated from CD63hi but not CD63lo beta cells into diabetic mice restores glucose homeostasis. These findings suggest that loss of a specific subset of beta cells may lead to diabetes. Strategies to reconstitute or maintain CD63hi beta cells may represent a potential anti-diabetic therapy.

DOI: 10.1038/s41556-023-01103-1

Source: https://www.nature.com/articles/s41556-023-01103-1

Nature Cell Biology:《自然—细胞生物学》,创刊于1999年。隶属于施普林格·自然出版集团,最新IF:28.213
官方网址:https://www.nature.com/ncb/
投稿链接:https://mts-ncb.nature.com/cgi-bin/main.plex


本期文章:《自然—细胞生物学》:Online/在线发表

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