| First Author | Zeng C | Year | 2014 |
| Journal | J Endocrinol | Volume | 223 |
| Issue | 3 | Pages | 277-87 |
| PubMed ID | 25287058 | Mgi Jnum | J:346260 |
| Mgi Id | MGI:6882577 | Doi | 10.1530/JOE-14-0509 |
| Citation | Zeng C, et al. (2014) RNase L contributes to experimentally induced type 1 diabetes onset in mice. J Endocrinol 223(3):277-87 |
| abstractText | The cause of type 1 diabetes continues to be a focus of investigation. Studies have revealed that interferon alpha (IFNalpha) in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type 1 diabetes. However, how IFNalpha contributes to the onset of type 1 diabetes is obscure. In this study, we found that 2-5A-dependent RNase L (RNase L), an IFNalpha-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type 1 diabetes. Using RNase L-deficient, rat insulin promoter-B7.1 transgenic mice, which are more vulnerable to harmful environmental factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin, a drug which can artificially induce type 1-like diabetes in experimental animals. Immunohistochemical staining results indicated that the population of infiltrated CD8(+)T cells was remarkably reduced in the islets of RNase L-deficient mice, indicating that RNase L may contribute to type 1 diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas under induced conditions. Our findings provide new insights into the molecular mechanism underlying beta-cell destruction and may indicate novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L. |
