Document Type
Article
Publication Date
12-1-2014
Publication Title
Journal of Endocrinology
Abstract
The cause of type 1 diabetes continues to be a focus of investigation. Studies have revealed that interferon α (IFNα) 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 IFNα contributes to the onset of type 1 diabetes is obscure. In this study, we found that 2-5A-dependent RNase L (RNase L), an IFNα-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 β-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.
Recommended Citation
Zeng, Chun; Yi, Xin; Zipris, Danny; Liu, Hongli; Zhang, Lin; Zheng, Qiaoyun; Malathi, Krishnamurthy; Jin, Ge; and Zhou, Aimin, "RNase L Contributes to Experimentally Induced Type 1 Diabetes Onset in Mice" (2014). Chemistry Faculty Publications. 404.
https://engagedscholarship.csuohio.edu/scichem_facpub/404
DOI
10.1530/JOE-14-0509
Version
Postprint
Volume
223
Issue
3
Comments
This work was supported by Marousch Award, the Diabetes Association of Greater Cleveland to A Z and partially by grants from the National Institutes of Health (R15DK084460-01A2) to A Z and (AI089518) to K M.