SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells

SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overex...

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Autores principales: Hu, Li, He, Fengli, Huang, Meifeng, Zhao, Qian, Cheng, Lamei, Said, Neveen, Zhou, Zhiguang, Liu, Feng, Dai, Yan-Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567887/
https://www.ncbi.nlm.nih.gov/pubmed/33067534
http://dx.doi.org/10.1038/s41598-020-74593-w
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author Hu, Li
He, Fengli
Huang, Meifeng
Zhao, Qian
Cheng, Lamei
Said, Neveen
Zhou, Zhiguang
Liu, Feng
Dai, Yan-Shan
author_facet Hu, Li
He, Fengli
Huang, Meifeng
Zhao, Qian
Cheng, Lamei
Said, Neveen
Zhou, Zhiguang
Liu, Feng
Dai, Yan-Shan
author_sort Hu, Li
collection PubMed
description SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors. Conversely, knockdown of SPARC up-regulated RGS4 in Min6 cells. RGS4 was up-regulated in islets from sparc −/− mice, which correlated with decreased glucose-stimulated insulin secretion (GSIS). Furthermore, inhibition of RGS4 restored GSIS in the islets from sparc −/− mice, and knockdown of RGS4 partially decreased the promoting effect of SPARC on oxotremorine-M-stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished SPARC-induced down-regulation of RGS4. Taken together, our data revealed that SPARC promoted GSIS by inhibiting RGS4 in pancreatic β cells.
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spelling pubmed-75678872020-10-19 SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells Hu, Li He, Fengli Huang, Meifeng Zhao, Qian Cheng, Lamei Said, Neveen Zhou, Zhiguang Liu, Feng Dai, Yan-Shan Sci Rep Article SPARC-deficient mice have been shown to exhibit impaired glucose tolerance and insulin secretion, but the underlying mechanism remains unknown. Here, we showed that SPARC enhanced the promoting effect of Muscarinic receptor agonist oxotremorine-M on insulin secretion in cultured mouse islets. Overexpression of SPARC down-regulated RGS4, a negative regulator of β-cell M3 muscarinic receptors. Conversely, knockdown of SPARC up-regulated RGS4 in Min6 cells. RGS4 was up-regulated in islets from sparc −/− mice, which correlated with decreased glucose-stimulated insulin secretion (GSIS). Furthermore, inhibition of RGS4 restored GSIS in the islets from sparc −/− mice, and knockdown of RGS4 partially decreased the promoting effect of SPARC on oxotremorine-M-stimulated insulin secretion. Phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 abolished SPARC-induced down-regulation of RGS4. Taken together, our data revealed that SPARC promoted GSIS by inhibiting RGS4 in pancreatic β cells. Nature Publishing Group UK 2020-10-16 /pmc/articles/PMC7567887/ /pubmed/33067534 http://dx.doi.org/10.1038/s41598-020-74593-w Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hu, Li
He, Fengli
Huang, Meifeng
Zhao, Qian
Cheng, Lamei
Said, Neveen
Zhou, Zhiguang
Liu, Feng
Dai, Yan-Shan
SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title_full SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title_fullStr SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title_full_unstemmed SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title_short SPARC promotes insulin secretion through down-regulation of RGS4 protein in pancreatic β cells
title_sort sparc promotes insulin secretion through down-regulation of rgs4 protein in pancreatic β cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567887/
https://www.ncbi.nlm.nih.gov/pubmed/33067534
http://dx.doi.org/10.1038/s41598-020-74593-w
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