Osteoprotegerin regulates pancreatic β-cell homeostasis upon microbial invasion

Yukiko Kuroda, Kenta Maruyama, Hideki Fujii, Isamu Sugawara, Shigeru B.H. Ko, Hisataka Yasuda, Hidenori Matsui, Koichi Matsuo

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0146544
JournalPloS one
Volume11
Issue number1
DOIs
Publication statusPublished - 2016 Jan 11

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Kuroda, Y., Maruyama, K., Fujii, H., Sugawara, I., Ko, S. B. H., Yasuda, H., Matsui, H., & Matsuo, K. (2016). Osteoprotegerin regulates pancreatic β-cell homeostasis upon microbial invasion. PloS one, 11(1), [e0146544]. https://doi.org/10.1371/journal.pone.0146544