Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners
Abstract Aims/Introduction Pancreatic β‐cells are sensitive to endoplasmic reticulum (ER) stress, which has a major role in the context of β‐cell death. Adrenomedullin (ADM) has been shown to exert a cytoprotective effect under various pathophysiological conditions. Several studies have suggested th...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-07-01
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| Series: | Journal of Diabetes Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jdi.13218 |
| _version_ | 1819094357535358976 |
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| author | Risa Suetomi Yasuharu Ohta Masaru Akiyama Takuro Matsumura Akihiko Taguchi Kaoru Yamamoto Takashi Kamatani Yukio Tanizawa |
| author_facet | Risa Suetomi Yasuharu Ohta Masaru Akiyama Takuro Matsumura Akihiko Taguchi Kaoru Yamamoto Takashi Kamatani Yukio Tanizawa |
| author_sort | Risa Suetomi |
| collection | DOAJ |
| description | Abstract Aims/Introduction Pancreatic β‐cells are sensitive to endoplasmic reticulum (ER) stress, which has a major role in the context of β‐cell death. Adrenomedullin (ADM) has been shown to exert a cytoprotective effect under various pathophysiological conditions. Several studies have suggested that thiazolidinediones have protective effects on β‐cells. During the course to elucidate the molecular mechanisms by which pioglitazone prevents β‐cell death, ADM emerged as a candidate. Here, we studied the regulation of ADM expression, including the effects of pioglitazone, and its role in pancreatic islets. Materials and Methods We analyzed ADM expression in islet cell lines treated with pioglitazone. The effects of ER stress on ADM and ADM receptor expressions were investigated by analyzing thapsigargin‐treated MIN6 cells and islets isolated from Wfs1−/− and db/db mice. To study the anti‐apoptotic effect of ADM, ER stress‐exposed MIN6 cells were treated with ADM peptides or transfected with ADM expression plasmid. Results Pioglitazone increased the production and secretion of ADM in islets through peroxisome‐proliferator activated receptor‐γ‐dependent mechanisms. Thapsigargin treatment increased expressions of both ADM and ADM receptor, composed of Ramp2, Ramp3 and Crlr, in MIN6 cells. ADM and ADM receptor expressions were also increased in isolated islets from Wfs1−/− and db/db mice. ADM peptides and ADM overexpression protected MIN6 cells from thapsigargin‐induced apoptosis. Conclusions ER stress stimulates ADM production and secretion in islets. ADM signaling might protect β‐cells from ER stress‐induced apoptosis, and might be one of the self‐protective mechanisms. β‐Cell protection by pioglitazone is partly through induction of ADM. ADM‐based therapy could be a novel strategy for treating diabetes. |
| first_indexed | 2024-12-21T23:26:07Z |
| format | Article |
| id | doaj.art-ff266980d0db4e78a9cd67535423995a |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-12-21T23:26:07Z |
| publishDate | 2020-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-ff266980d0db4e78a9cd67535423995a2022-12-21T18:46:37ZengWileyJournal of Diabetes Investigation2040-11162040-11242020-07-0111482383310.1111/jdi.13218Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine mannersRisa Suetomi0Yasuharu Ohta1Masaru Akiyama2Takuro Matsumura3Akihiko Taguchi4Kaoru Yamamoto5Takashi Kamatani6Yukio Tanizawa7Division of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanDivision of Endocrinology, Metabolism, Hematological Science and Therapeutics Department of Bio‐Signal Analysis Graduate School of Medicine Yamaguchi University Ube JapanAbstract Aims/Introduction Pancreatic β‐cells are sensitive to endoplasmic reticulum (ER) stress, which has a major role in the context of β‐cell death. Adrenomedullin (ADM) has been shown to exert a cytoprotective effect under various pathophysiological conditions. Several studies have suggested that thiazolidinediones have protective effects on β‐cells. During the course to elucidate the molecular mechanisms by which pioglitazone prevents β‐cell death, ADM emerged as a candidate. Here, we studied the regulation of ADM expression, including the effects of pioglitazone, and its role in pancreatic islets. Materials and Methods We analyzed ADM expression in islet cell lines treated with pioglitazone. The effects of ER stress on ADM and ADM receptor expressions were investigated by analyzing thapsigargin‐treated MIN6 cells and islets isolated from Wfs1−/− and db/db mice. To study the anti‐apoptotic effect of ADM, ER stress‐exposed MIN6 cells were treated with ADM peptides or transfected with ADM expression plasmid. Results Pioglitazone increased the production and secretion of ADM in islets through peroxisome‐proliferator activated receptor‐γ‐dependent mechanisms. Thapsigargin treatment increased expressions of both ADM and ADM receptor, composed of Ramp2, Ramp3 and Crlr, in MIN6 cells. ADM and ADM receptor expressions were also increased in isolated islets from Wfs1−/− and db/db mice. ADM peptides and ADM overexpression protected MIN6 cells from thapsigargin‐induced apoptosis. Conclusions ER stress stimulates ADM production and secretion in islets. ADM signaling might protect β‐cells from ER stress‐induced apoptosis, and might be one of the self‐protective mechanisms. β‐Cell protection by pioglitazone is partly through induction of ADM. ADM‐based therapy could be a novel strategy for treating diabetes.https://doi.org/10.1111/jdi.13218AdrenomedullinApoptosisPancreatic islet |
| spellingShingle | Risa Suetomi Yasuharu Ohta Masaru Akiyama Takuro Matsumura Akihiko Taguchi Kaoru Yamamoto Takashi Kamatani Yukio Tanizawa Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners Journal of Diabetes Investigation Adrenomedullin Apoptosis Pancreatic islet |
| title | Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners |
| title_full | Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners |
| title_fullStr | Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners |
| title_full_unstemmed | Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners |
| title_short | Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β‐cells in autocrine and paracrine manners |
| title_sort | adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β cells in autocrine and paracrine manners |
| topic | Adrenomedullin Apoptosis Pancreatic islet |
| url | https://doi.org/10.1111/jdi.13218 |
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