title: Interleukin-1β-Targeted Vaccine Improves Glucose Control and β-Cell Function in a Diabetic KK-Ay Mouse Model.
abstract: Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP 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, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.|School of Pharmacy, China Pharmaceutical University, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zha
authors.affiliation: Weifang Biomedical Innovation and Entrepreneurship Service Center, Weifang, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Chi
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Yu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.|School of Bioengineering, Qilu University of Technology, Jinan, China.
authors.forename: Xiang-Meng
authors.initials: XM
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Dong-Qun
authors.initials: DQ
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ji
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China.
authors.forename: Rui-Tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000517:prevention & control; D007333:Insulin Resistance; D053583:Interleukin-1beta / Q000378:metabolism*; D007515:Islets of Langerhans / Q000503:physiopathology*; D051379:Mice; D014612:Vaccines / Q000008:administration & dosage*; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D053583:Interleukin-1beta; D014612:Vaccines