Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics

Abstract GLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still...

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Autores principales:	Jia-shu Tang, Qing-run Li, Jia-ming Li, Jia-rui Wu, Rong Zeng
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6d3926a792894f9e88ffe8e68d2075cf
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spelling	oai:doaj.org-article:6d3926a792894f9e88ffe8e68d2075cf2021-12-02T11:52:39ZSystematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics10.1038/s41598-017-00841-12045-2322https://doaj.org/article/6d3926a792894f9e88ffe8e68d2075cf2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00841-1https://doaj.org/toc/2045-2322Abstract GLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still limited. Here we performed a quantitative phosphoproteomics study to systematically present the synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP-1. We generated the largest pancreatic β-cell phosphoproteome by identifying 25,327 accurately localized phosphorylation sites on 5,389 proteins. Our results discovered several novel kinases regulated by glucose, GLP-1 or their synergism, and some of these kinases might act as downstream molecules of GLP-1 mediated PKA signaling cascade. A few phosphosites were regulated by both GLP-1 and glucose alone, and these target proteins were highly related to their biological function on pancreatic β-cells. Finally, we found glucose and GLP-1 executed their synergistic effect at multiple levels, especially at pathway level. Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion.Jia-shu TangQing-run LiJia-ming LiJia-rui WuRong ZengNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jia-shu Tang Qing-run Li Jia-ming Li Jia-rui Wu Rong Zeng Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
description	Abstract GLP-1 synergizes with glucose in regulating pancreatic β-cell function, including facilitating β-cell survival and insulin secretion. Though it has been widely accepted that phosphorylation is extremely important in regulating β-cell functions, our knowledge to the global mechanism is still limited. Here we performed a quantitative phosphoproteomics study to systematically present the synergistic regulation of INS-1E cell phosphoproteome mediated by glucose and GLP-1. We generated the largest pancreatic β-cell phosphoproteome by identifying 25,327 accurately localized phosphorylation sites on 5,389 proteins. Our results discovered several novel kinases regulated by glucose, GLP-1 or their synergism, and some of these kinases might act as downstream molecules of GLP-1 mediated PKA signaling cascade. A few phosphosites were regulated by both GLP-1 and glucose alone, and these target proteins were highly related to their biological function on pancreatic β-cells. Finally, we found glucose and GLP-1 executed their synergistic effect at multiple levels, especially at pathway level. Both GLP-1 and glucose participated in regulating every single step of the secretion pathway, and systematically synergized their effects in inducing insulin secretion.
format	article
author	Jia-shu Tang Qing-run Li Jia-ming Li Jia-rui Wu Rong Zeng
author_facet	Jia-shu Tang Qing-run Li Jia-ming Li Jia-rui Wu Rong Zeng
author_sort	Jia-shu Tang
title	Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
title_short	Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
title_full	Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
title_fullStr	Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
title_full_unstemmed	Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics
title_sort	systematic synergy of glucose and glp-1 to stimulate insulin secretion revealed by quantitative phosphoproteomics
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6d3926a792894f9e88ffe8e68d2075cf
work_keys_str_mv	AT jiashutang systematicsynergyofglucoseandglp1tostimulateinsulinsecretionrevealedbyquantitativephosphoproteomics AT qingrunli systematicsynergyofglucoseandglp1tostimulateinsulinsecretionrevealedbyquantitativephosphoproteomics AT jiamingli systematicsynergyofglucoseandglp1tostimulateinsulinsecretionrevealedbyquantitativephosphoproteomics AT jiaruiwu systematicsynergyofglucoseandglp1tostimulateinsulinsecretionrevealedbyquantitativephosphoproteomics AT rongzeng systematicsynergyofglucoseandglp1tostimulateinsulinsecretionrevealedbyquantitativephosphoproteomics
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Systematic Synergy of Glucose and GLP-1 to Stimulate Insulin Secretion Revealed by Quantitative Phosphoproteomics

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