小分子诱导胰岛α细胞胰岛素表达。
Small-molecule inducers of insulin expression in pancreatic alpha-cells.
机构信息
Howard Hughes Medical Institute, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142.
出版信息
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15099-104. doi: 10.1073/pnas.1010018107. Epub 2010 Aug 9.
Abstract
High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused alpha-cells to adopt several morphological and gene expression features of a beta-cell state. Assay-performance profile analysis suggests kinase inhibition as a mechanism of action, and we show that biochemical and cellular inhibition of the RSK kinase family by BRD7389 is likely related to its ability induce a beta-cell-like state. BRD7389 also increases the endocrine cell content and function of donor human pancreatic islets in culture.
摘要
高内涵筛选小分子胰岛素诱导物鉴定出化合物 BRD7389，它使 alpha 细胞呈现出几种 beta 细胞状态的形态和基因表达特征。分析表明该化合物的作用机制可能是抑制激酶，我们还证明 BRD7389 通过抑制 RSK 激酶家族的生化和细胞活性与其诱导 beta 样细胞状态的能力有关。BRD7389 还能增加培养物中供体人胰岛内分泌细胞的含量和功能。
相似文献
1
Small-molecule inducers of insulin expression in pancreatic alpha-cells.小分子诱导胰岛α细胞胰岛素表达。
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15099-104. doi: 10.1073/pnas.1010018107. Epub 2010 Aug 9.
2
Processing of proglucagon to GLP-1 in pancreatic α-cells: is this a paracrine mechanism enabling GLP-1 to act on β-cells?胰脏α细胞中胰高血糖素原向 GLP-1 的加工：这是否是一种允许 GLP-1 作用于β细胞的旁分泌机制？
J Endocrinol. 2011 Oct;211(1):99-106. doi: 10.1530/JOE-11-0094. Epub 2011 Jul 27.
3
Glucagon-Like Peptide 1 Increases β-Cell Regeneration by Promoting α- to β-Cell Transdifferentiation.胰高血糖素样肽 1 通过促进α细胞到β细胞转分化增加β细胞再生。
Diabetes. 2018 Dec;67(12):2601-2614. doi: 10.2337/db18-0155. Epub 2018 Sep 26.
4
Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.差异表达的微小RNA-483在胰腺β细胞和α细胞中发挥不同功能。
J Biol Chem. 2015 Aug 7;290(32):19955-66. doi: 10.1074/jbc.M115.650705. Epub 2015 Jun 24.
5
Expression and function of cannabinoid receptors in mouse islets.大麻素受体在小鼠胰岛中的表达和功能。
Islets. 2010 Sep-Oct;2(5):293-302. doi: 10.4161/isl.2.5.12729. Epub 2010 Sep 1.
6
Improvement of pig islet function by in vivo pancreatic tissue remodeling: a "human-like" pig islet structure with streptozotocin treatment.通过体内胰腺组织重塑改善猪胰岛功能：用链脲佐菌素处理的“类人”猪胰岛结构。
Cell Transplant. 2013;22(11):2161-73. doi: 10.3727/096368912X657864. Epub 2012 Oct 8.
7
Activins A and B Regulate Fate-Determining Gene Expression in Islet Cell Lines and Islet Cells From Male Mice.激活素A和B调节雄性小鼠胰岛细胞系和胰岛细胞中决定命运的基因表达。
Endocrinology. 2015 Jul;156(7):2440-50. doi: 10.1210/en.2015-1167. Epub 2015 May 11.
8
Differences between amyloid toxicity in alpha and beta cells in human and mouse islets and the role of caspase-3.胰岛中α和β细胞中淀粉样毒性的差异以及半胱天冬酶-3的作用。
Diabetologia. 2010 Jul;53(7):1415-27. doi: 10.1007/s00125-010-1717-9. Epub 2010 Apr 6.
9
Automated recognition and quantification of pancreatic islets in Zucker diabetic fatty rats treated with exendin-4.自动化识别和定量分析接受 exendin-4 治疗的 Zucker 糖尿病肥胖大鼠的胰岛。
J Endocrinol. 2013 Jan 2;216(1):13-20. doi: 10.1530/JOE-12-0456. Print 2013 Jan.
10
Immunohistochemical study of α- and β-cell distribution in human pancreatic Langerhans islets of various types.不同类型人胰腺朗格汉斯胰岛中α细胞和β细胞分布的免疫组织化学研究。
Bull Exp Biol Med. 2013 Oct;155(6):798-801. doi: 10.1007/s10517-013-2255-5.
引用本文的文献
1
Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.线粒体特征塑造了对PLK1抑制剂的表型转换和细胞凋亡。
Life Sci Alliance. 2024 Dec 10;8(3). doi: 10.26508/lsa.202402912. Print 2025 Mar.
2
Stimulation of insulin secretion induced by low 4-cresol dose involves the RPS6KA3 signalling pathway.低浓度 4-甲酚诱导的胰岛素分泌刺激涉及 RPS6KA3 信号通路。
PLoS One. 2024 Oct 24;19(10):e0310370. doi: 10.1371/journal.pone.0310370. eCollection 2024.
3
Activation of MAP Kinase Pathway by Polyisoprenylated Cysteinyl Amide Inhibitors Causes Apoptosis and Disrupts Breast Cancer Cell Invasion.聚异戊二烯化半胱氨酰胺抑制剂激活丝裂原活化蛋白激酶途径可导致细胞凋亡并破坏乳腺癌细胞的侵袭能力。
Biomedicines. 2024 Feb 20;12(3):470. doi: 10.3390/biomedicines12030470.
4
Therapeutic targeting of p90 ribosomal S6 kinase.p90核糖体S6激酶的治疗靶点
Front Cell Dev Biol. 2023 Dec 19;11:1297292. doi: 10.3389/fcell.2023.1297292. eCollection 2023.
5
Dissecting the molecular trajectory of fibroblast reprogramming to chemically induced mammary epithelial cells.剖析成纤维细胞重编程为化学诱导乳腺上皮细胞的分子轨迹。
Front Cell Dev Biol. 2023 Aug 2;11:1194070. doi: 10.3389/fcell.2023.1194070. eCollection 2023.
6
The RSK2-RPS6 axis promotes axonal regeneration in the peripheral and central nervous systems.RSK2-RPS6 轴促进周围和中枢神经系统中的轴突再生。
PLoS Biol. 2023 Apr 17;21(4):e3002044. doi: 10.1371/journal.pbio.3002044. eCollection 2023 Apr.
7
Artemether treatment improves islet function and metabolic homeostasis in diabetic nonhuman primates.青蒿素治疗可改善糖尿病非人灵长类动物的胰岛功能和代谢稳态。
J Diabetes. 2023 Jan;15(1):76-80. doi: 10.1111/1753-0407.13347. Epub 2023 Jan 9.
8
Reprogramming-Evolving Path to Functional Surrogate β-Cells.重编程——功能性替代β细胞的进化之路。
Cells. 2022 Sep 8;11(18):2813. doi: 10.3390/cells11182813.
9
Cell Transdifferentiation and Reprogramming in Disease Modeling: Insights into the Neuronal and Cardiac Disease Models and Current Translational Strategies.细胞转分化和重编程在疾病建模中的作用：对神经和心脏疾病模型的深入了解以及当前的转化策略。
Cells. 2021 Sep 27;10(10):2558. doi: 10.3390/cells10102558.
10
Debates in Pancreatic Beta Cell Biology: Proliferation Versus Progenitor Differentiation and Transdifferentiation in Restoring β Cell Mass.胰腺β 细胞生物学的争论：增殖与祖细胞分化和转分化在恢复β 细胞质量中的作用。
Front Endocrinol (Lausanne). 2021 Aug 6;12:722250. doi: 10.3389/fendo.2021.722250. eCollection 2021.
本文引用的文献
1
Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.成年胰腺α细胞在β细胞大量缺失后向β细胞的转化。
Nature. 2010 Apr 22;464(7292):1149-54. doi: 10.1038/nature08894. Epub 2010 Apr 4.
2
How to make beta cells?如何生成胰岛β细胞？
Curr Opin Cell Biol. 2009 Dec;21(6):727-32. doi: 10.1016/j.ceb.2009.08.006. Epub 2009 Sep 24.
3
The ectopic expression of Pax4 in the mouse pancreas converts progenitor cells into alpha and subsequently beta cells.Pax4在小鼠胰腺中的异位表达可将祖细胞转化为α细胞，随后再转化为β细胞。
Cell. 2009 Aug 7;138(3):449-62. doi: 10.1016/j.cell.2009.05.035.
4
Extreme makeover: converting one cell into another.极端改造：将一种细胞转化为另一种细胞。
Cell Stem Cell. 2008 Oct 9;3(4):382-8. doi: 10.1016/j.stem.2008.09.015.
5
Targeting RSK: an overview of small molecule inhibitors.靶向RSK：小分子抑制剂概述
Anticancer Agents Med Chem. 2008 Oct;8(7):710-6. doi: 10.2174/187152008785914770.
6
The RSK family of kinases: emerging roles in cellular signalling.RSK激酶家族：在细胞信号传导中的新作用。
Nat Rev Mol Cell Biol. 2008 Oct;9(10):747-58. doi: 10.1038/nrm2509.
7
Promoting ectopic pancreatic fates: pancreas development and future diabetes therapies.促进异位胰腺命运：胰腺发育与未来糖尿病治疗
Clin Genet. 2008 Oct;74(4):316-24. doi: 10.1111/j.1399-0004.2008.01081.x. Epub 2008 Sep 9.
8
In vivo reprogramming of adult pancreatic exocrine cells to beta-cells.成年胰腺外分泌细胞在体内重编程为β细胞。
Nature. 2008 Oct 2;455(7213):627-32. doi: 10.1038/nature07314. Epub 2008 Aug 27.
9
The RSK factors of activating the Ras/MAPK signaling cascade.激活Ras/MAPK信号级联反应的RSK因子。
Front Biosci. 2008 May 1;13:4258-75. doi: 10.2741/3003.
10
Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo.源自人类胚胎干细胞的胰腺内胚层在体内生成对葡萄糖有反应的胰岛素分泌细胞。
Nat Biotechnol. 2008 Apr;26(4):443-52. doi: 10.1038/nbt1393. Epub 2008 Feb 20.
Zotero 插件