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Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway
Prostasin (PRSS8) is a serine protease that metabolizes and moderates the effect of specific substrates. Epidermal growth factor receptor (EGFR), which modulates insulin secretion and pancreatic β-cell proliferation, is regulated via proteolytic shedding by PRSS8. We first detected PRSS8 expression...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241893/ https://www.ncbi.nlm.nih.gov/pubmed/37277555 http://dx.doi.org/10.1038/s41598-023-36326-7 |
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author | Ishii, Toshihisa Miyasato, Yoshikazu Ichijo, Masashi Uchimura, Kohei Furuya, Fumihiko |
author_facet | Ishii, Toshihisa Miyasato, Yoshikazu Ichijo, Masashi Uchimura, Kohei Furuya, Fumihiko |
author_sort | Ishii, Toshihisa |
collection | PubMed |
description | Prostasin (PRSS8) is a serine protease that metabolizes and moderates the effect of specific substrates. Epidermal growth factor receptor (EGFR), which modulates insulin secretion and pancreatic β-cell proliferation, is regulated via proteolytic shedding by PRSS8. We first detected PRSS8 expression in β-cells of pancreatic islets of mice. To better understand the molecular processes involved in PRSS8-associated insulin secretion, pancreatic β-cell-specific PRSS8 knockout (βKO) and PRSS8-overexpressing (βTG) male mice were generated. We found that glucose intolerance and reduction in glucose-stimulated insulin secretion developed in βKO mice compared with the control subjects. A higher response to glucose was noted in islets retrieved from βTG mice. Erlotinib, a specific blocker of EGFR, blocks EGF- and glucose-stimulated secretion of insulin among MIN6 cells, and glucose improves EGF release from β-cells. After silencing PRSS8 in MIN6 cells, glucose-stimulated insulin secretion decreased, and EGFR signaling was impaired. Conversely, overexpression of PRSS8 in MIN6 cells induced higher concentrations of both basal and glucose-stimulated insulin secretion and increased phospho-EGFR concentrations. Furthermore, short-term exposure to glucose improved the concentration of endogenous PRSS8 in MIN6 cells through inhibition of intracellular degradation. These findings suggest that PRSS8 is involved in glucose-dependent physiological regulation of insulin secretion via the EGF–EGFR signaling pathway in pancreatic β-cells. |
format | Online Article Text |
id | pubmed-10241893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102418932023-06-07 Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway Ishii, Toshihisa Miyasato, Yoshikazu Ichijo, Masashi Uchimura, Kohei Furuya, Fumihiko Sci Rep Article Prostasin (PRSS8) is a serine protease that metabolizes and moderates the effect of specific substrates. Epidermal growth factor receptor (EGFR), which modulates insulin secretion and pancreatic β-cell proliferation, is regulated via proteolytic shedding by PRSS8. We first detected PRSS8 expression in β-cells of pancreatic islets of mice. To better understand the molecular processes involved in PRSS8-associated insulin secretion, pancreatic β-cell-specific PRSS8 knockout (βKO) and PRSS8-overexpressing (βTG) male mice were generated. We found that glucose intolerance and reduction in glucose-stimulated insulin secretion developed in βKO mice compared with the control subjects. A higher response to glucose was noted in islets retrieved from βTG mice. Erlotinib, a specific blocker of EGFR, blocks EGF- and glucose-stimulated secretion of insulin among MIN6 cells, and glucose improves EGF release from β-cells. After silencing PRSS8 in MIN6 cells, glucose-stimulated insulin secretion decreased, and EGFR signaling was impaired. Conversely, overexpression of PRSS8 in MIN6 cells induced higher concentrations of both basal and glucose-stimulated insulin secretion and increased phospho-EGFR concentrations. Furthermore, short-term exposure to glucose improved the concentration of endogenous PRSS8 in MIN6 cells through inhibition of intracellular degradation. These findings suggest that PRSS8 is involved in glucose-dependent physiological regulation of insulin secretion via the EGF–EGFR signaling pathway in pancreatic β-cells. Nature Publishing Group UK 2023-06-05 /pmc/articles/PMC10241893/ /pubmed/37277555 http://dx.doi.org/10.1038/s41598-023-36326-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ishii, Toshihisa Miyasato, Yoshikazu Ichijo, Masashi Uchimura, Kohei Furuya, Fumihiko Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title | Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title_full | Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title_fullStr | Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title_full_unstemmed | Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title_short | Membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
title_sort | membrane protease prostasin promotes insulin secretion by regulating the epidermal growth factor receptor pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10241893/ https://www.ncbi.nlm.nih.gov/pubmed/37277555 http://dx.doi.org/10.1038/s41598-023-36326-7 |
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