Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R

Abstract Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone...

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Autores principales:	Geetali Pradhan, Chia-Shan Wu, Jong Han Lee, Preeti Kanikarla, Shaodong Guo, Vijay K. Yechoor, Susan L. Samson, Yuxiang Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b735f08e0564ebead1027bd8a844987
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spelling	oai:doaj.org-article:1b735f08e0564ebead1027bd8a8449872021-12-02T16:06:38ZObestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R10.1038/s41598-017-00888-02045-2322https://doaj.org/article/1b735f08e0564ebead1027bd8a8449872017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00888-0https://doaj.org/toc/2045-2322Abstract Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin −/− mice. Surprisingly, obestatin-induced GSIS was absent in β-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr −/− mice, and in pancreatic islets isolated from Ghsr −/− mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from β-cell-specific Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin’s effect on insulin secretion is mediated by GHS-R in pancreatic β-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.Geetali PradhanChia-Shan WuJong Han LeePreeti KanikarlaShaodong GuoVijay K. YechoorSusan L. SamsonYuxiang SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Geetali Pradhan Chia-Shan Wu Jong Han Lee Preeti Kanikarla Shaodong Guo Vijay K. Yechoor Susan L. Samson Yuxiang Sun Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
description	Abstract Orexigenic hormone ghrelin and anorexic hormone obestatin are encoded by the same preproghrelin gene. While it is known that ghrelin inhibits glucose-stimulated insulin secretion (GSIS), the effect of obestatin on GSIS is unclear. Ghrelin’s effect is mediated by its receptor Growth Hormone Secretagogue Receptor (GHS-R), but the physiologically relevant receptor of obestatin remains debatable. Here we have investigated the effect of obestatin on GSIS in vitro, in vivo and ex vivo, and tested whether obestatin regulates insulin secretion through GHS-R. We found that under hyperglycemic condition, obestatin augments GSIS in rat insulinoma cells (INS-1) and in pancreatic islets from ghrelin −/− mice. Surprisingly, obestatin-induced GSIS was absent in β-cells in which GHS-R was suppressed. Obestatin-induced insulin secretion was abolished in the circulation of Ghsr −/− mice, and in pancreatic islets isolated from Ghsr −/− mice. We also found that obestatin-induced GSIS was attenuated in islets isolated from β-cell-specific Ghsr knockout MIP-Cre/ERT;Ghsrf/f mice. Our data collectively demonstrate that obestatin is a potent insulin secretagogue under hyperglycemic condition, and obestatin’s effect on insulin secretion is mediated by GHS-R in pancreatic β-cells. Our findings reveal an intriguing insight that obestatin and ghrelin have opposing effects on insulin secretion, and both are mediated through ghrelin receptor GHS-R.
format	article
author	Geetali Pradhan Chia-Shan Wu Jong Han Lee Preeti Kanikarla Shaodong Guo Vijay K. Yechoor Susan L. Samson Yuxiang Sun
author_facet	Geetali Pradhan Chia-Shan Wu Jong Han Lee Preeti Kanikarla Shaodong Guo Vijay K. Yechoor Susan L. Samson Yuxiang Sun
author_sort	Geetali Pradhan
title	Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
title_short	Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
title_full	Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
title_fullStr	Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
title_full_unstemmed	Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R
title_sort	obestatin stimulates glucose-induced insulin secretion through ghrelin receptor ghs-r
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1b735f08e0564ebead1027bd8a844987
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Obestatin stimulates glucose-induced insulin secretion through ghrelin receptor GHS-R

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