| First Author | Kuroda Y | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 1 | Pages | e0146544 |
| PubMed ID | 26751951 | Mgi Jnum | J:269165 |
| Mgi Id | MGI:6092828 | Doi | 10.1371/journal.pone.0146544 |
| Citation | Kuroda Y, et al. (2016) Osteoprotegerin Regulates Pancreatic beta-Cell Homeostasis upon Microbial Invasion. PLoS One 11(1):e0146544 |
| abstractText | Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-kappaB 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 beta-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 beta-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 beta-cell homeostasis by restricting glucose-stimulated insulin secretion, possibly preventing microbe-induced exhaustion of beta-cell secretory capacity. |
