Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion.
Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), antagonizes RANKL's osteoclastogenic function in bone. We previously demonstrated that systemic administration of lipopolysaccharide (LPS) to mice elevates OPG levels and reduces RANKL levels in peripheral b...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4709133?pdf=render |
| _version_ | 1818318817891188736 |
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| author | Yukiko Kuroda Kenta Maruyama Hideki Fujii Isamu Sugawara Shigeru B H Ko Hisataka Yasuda Hidenori Matsui Koichi Matsuo |
| author_facet | Yukiko Kuroda Kenta Maruyama Hideki Fujii Isamu Sugawara Shigeru B H Ko Hisataka Yasuda Hidenori Matsui Koichi Matsuo |
| author_sort | Yukiko Kuroda |
| collection | DOAJ |
| description | Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), antagonizes RANKL's osteoclastogenic function in bone. We previously demonstrated that systemic administration of lipopolysaccharide (LPS) to mice elevates OPG levels and reduces RANKL levels in peripheral blood. Here, we show that mice infected with Salmonella, Staphylococcus, Mycobacteria or influenza virus also show elevated serum OPG levels. We then asked whether OPG upregulation following microbial invasion had an effect outside of bone. To do so, we treated mice with LPS and observed OPG production in pancreas, especially in β-cells of pancreatic islets. Insulin release following LPS administration was enhanced in mice lacking OPG, suggesting that OPG inhibits insulin secretion under acute inflammatory conditions. Consistently, treatment of MIN6 pancreatic β-cells with OPG decreased their insulin secretion following glucose stimulation in the presence of LPS. Finally, our findings suggest that LPS-induced OPG upregulation is mediated in part by activator protein (AP)-1 family transcription factors, particularly Fos proteins. Overall, we report that acute microbial infection elevates serum OPG, which maintains β-cell homeostasis by restricting glucose-stimulated insulin secretion, possibly preventing microbe-induced exhaustion of β-cell secretory capacity. |
| first_indexed | 2024-12-13T09:59:15Z |
| format | Article |
| id | doaj.art-c7fe118a43da431faca26153b807a1b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T09:59:15Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c7fe118a43da431faca26153b807a1b02022-12-21T23:51:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014654410.1371/journal.pone.0146544Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion.Yukiko KurodaKenta MaruyamaHideki FujiiIsamu SugawaraShigeru B H KoHisataka YasudaHidenori MatsuiKoichi MatsuoOsteoprotegerin (OPG), a decoy receptor for receptor activator of NF-κB ligand (RANKL), antagonizes RANKL's osteoclastogenic function in bone. We previously demonstrated that systemic administration of lipopolysaccharide (LPS) to mice elevates OPG levels and reduces RANKL levels in peripheral blood. Here, we show that mice infected with Salmonella, Staphylococcus, Mycobacteria or influenza virus also show elevated serum OPG levels. We then asked whether OPG upregulation following microbial invasion had an effect outside of bone. To do so, we treated mice with LPS and observed OPG production in pancreas, especially in β-cells of pancreatic islets. Insulin release following LPS administration was enhanced in mice lacking OPG, suggesting that OPG inhibits insulin secretion under acute inflammatory conditions. Consistently, treatment of MIN6 pancreatic β-cells with OPG decreased their insulin secretion following glucose stimulation in the presence of LPS. Finally, our findings suggest that LPS-induced OPG upregulation is mediated in part by activator protein (AP)-1 family transcription factors, particularly Fos proteins. Overall, we report that acute microbial infection elevates serum OPG, which maintains β-cell homeostasis by restricting glucose-stimulated insulin secretion, possibly preventing microbe-induced exhaustion of β-cell secretory capacity.http://europepmc.org/articles/PMC4709133?pdf=render |
| spellingShingle | Yukiko Kuroda Kenta Maruyama Hideki Fujii Isamu Sugawara Shigeru B H Ko Hisataka Yasuda Hidenori Matsui Koichi Matsuo Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. PLoS ONE |
| title | Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. |
| title_full | Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. |
| title_fullStr | Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. |
| title_full_unstemmed | Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. |
| title_short | Osteoprotegerin Regulates Pancreatic β-Cell Homeostasis upon Microbial Invasion. |
| title_sort | osteoprotegerin regulates pancreatic β cell homeostasis upon microbial invasion |
| url | http://europepmc.org/articles/PMC4709133?pdf=render |
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