Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

Abstract Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion...

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Autores principales:	Dongsheng Guo, Haikun Liu, Aynisahan Ruzi, Ge Gao, Abbas Nasir, Yanli Liu, Fan Yang, Feima Wu, Guosheng Xu, Yin-xiong Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2eef6fa0dafc4b3492d08947d95ff76c
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spelling	oai:doaj.org-article:2eef6fa0dafc4b3492d08947d95ff76c2021-12-02T15:06:21ZModeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas910.1038/s41598-017-03349-w2045-2322https://doaj.org/article/2eef6fa0dafc4b3492d08947d95ff76c2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03349-whttps://doaj.org/toc/2045-2322Abstract Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8-deficient stem cells generated by the CRISPR/Cas9 system. ABCC8-deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs.Dongsheng GuoHaikun LiuAynisahan RuziGe GaoAbbas NasirYanli LiuFan YangFeima WuGuosheng XuYin-xiong LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Dongsheng Guo Haikun Liu Aynisahan Ruzi Ge Gao Abbas Nasir Yanli Liu Fan Yang Feima Wu Guosheng Xu Yin-xiong Li Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
description	Abstract Congenital hyperinsulinism (CHI) is a rare genetic disorder characterized by excess insulin secretion, which results in hypoglycemia. Mutation of sulfonylurea receptor 1 (SUR1), encoded by the ABCC8 gene, is the main cause of CHI. Here, we captured the phenotype of excess insulin secretion through pancreatic differentiation of ABCC8-deficient stem cells generated by the CRISPR/Cas9 system. ABCC8-deficient insulin-producing cells secreted higher insulin than their wild-type counterparts, and the excess insulin secretion was rescued by nifedipine, octreotide and nicorandil. Further, we tested the role of SUR1 in response to different potassium levels and found that dysfunction of SUR1 decreased the insulin secretion rate in low and high potassium environments. Hence, pancreatic differentiation of ABCC8-deficient cells recapitulated the CHI disease phenotype in vitro, which represents an attractive model to further elucidate the function of SUR1 and to develop and screen for novel therapeutic drugs.
format	article
author	Dongsheng Guo Haikun Liu Aynisahan Ruzi Ge Gao Abbas Nasir Yanli Liu Fan Yang Feima Wu Guosheng Xu Yin-xiong Li
author_facet	Dongsheng Guo Haikun Liu Aynisahan Ruzi Ge Gao Abbas Nasir Yanli Liu Fan Yang Feima Wu Guosheng Xu Yin-xiong Li
author_sort	Dongsheng Guo
title	Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
title_short	Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
title_full	Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
title_fullStr	Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
title_full_unstemmed	Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9
title_sort	modeling congenital hyperinsulinism with abcc8-deficient human embryonic stem cells generated by crispr/cas9
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2eef6fa0dafc4b3492d08947d95ff76c
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Modeling Congenital Hyperinsulinism with ABCC8-Deficient Human Embryonic Stem Cells Generated by CRISPR/Cas9

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