| First Author | Zha J | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 5 | Pages | e0154298 |
| PubMed ID | 27152706 | Mgi Jnum | J:252484 |
| Mgi Id | MGI:6094684 | Doi | 10.1371/journal.pone.0154298 |
| Citation | Zha J, et al. (2016) Interleukin-1beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a Diabetic KK-Ay Mouse Model. PLoS One 11(5):e0154298 |
| abstractText | Interleukin-1beta (IL-1beta) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1beta impairs islet function by inducing insulin resistance and beta-cell apoptosis. Therefore, specifically reducing IL-1beta activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1beta-mediated islet inflammation. In this study, we developed an IL-1beta-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1betaEPP) and applied it to a diabetic KK-Ay mouse model. Results showed that the 1betaEPP elicited high antibody responses, which neutralized the biological activity of IL-1beta, and induced barely detectable inflammatory activity. 1betaEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1betaEPP restored beta-cell mass; inhibited beta-cell apoptosis; decreased the expression of IL-1beta; and interrupted NF-kappaB activation by reducing IKKbeta and pRelA levels. These studies indicated that the IL-1beta-targeted vaccine may be a promising immunotherapeutic for T2DM treatment. |
