PMID- 27152706
OWN - NLM
STAT- MEDLINE
DCOM- 20170711
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 5
DP  - 2016
TI  - Interleukin-1beta-Targeted Vaccine Improves Glucose Control and beta-Cell Function in a 
      Diabetic KK-Ay Mouse Model.
PG  - e0154298
LID - 10.1371/journal.pone.0154298 [doi]
LID - e0154298
AB  - 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.
FAU - Zha, Jun
AU  - Zha J
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
AD  - School of Pharmacy, China Pharmaceutical University, Nanjing, China.
FAU - Chi, Xiao-Wei
AU  - Chi XW
AD  - Weifang Biomedical Innovation and Entrepreneurship Service Center, Weifang, 
      China.
FAU - Yu, Xiao-Lin
AU  - Yu XL
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
FAU - Liu, Xiang-Meng
AU  - Liu XM
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
AD  - School of Bioengineering, Qilu University of Technology, Jinan, China.
FAU - Liu, Dong-Qun
AU  - Liu DQ
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
FAU - Zhu, Jie
AU  - Zhu J
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
FAU - Ji, Hui
AU  - Ji H
AD  - School of Pharmacy, China Pharmaceutical University, Nanjing, China.
FAU - Liu, Rui-Tian
AU  - Liu RT
AD  - National Key Laboratory of Biochemical Engineering, Institute of Process 
      Engineering, Chinese Academy of Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160506
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Blood Glucose)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Vaccines)
SB  - IM
MH  - Animals
MH  - Antibody Formation
MH  - Blood Glucose/*metabolism
MH  - Diabetes Mellitus, Experimental/*physiopathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glucose Tolerance Test
MH  - Hyperglycemia/prevention & control
MH  - Insulin Resistance
MH  - Interleukin-1beta/*metabolism
MH  - Islets of Langerhans/*physiopathology
MH  - Mice
MH  - Vaccines/*administration & dosage
MH  - Weight Gain
PMC - PMC4859560
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/05/07 06:00
MHDA- 2017/07/14 06:00
PMCR- 2016/05/06
CRDT- 2016/05/07 06:00
PHST- 2015/11/18 00:00 [received]
PHST- 2016/04/12 00:00 [accepted]
PHST- 2016/05/07 06:00 [entrez]
PHST- 2016/05/07 06:00 [pubmed]
PHST- 2017/07/14 06:00 [medline]
PHST- 2016/05/06 00:00 [pmc-release]
AID - PONE-D-15-50309 [pii]
AID - 10.1371/journal.pone.0154298 [doi]
PST - epublish
SO  - PLoS One. 2016 May 6;11(5):e0154298. doi: 10.1371/journal.pone.0154298. 
      eCollection 2016.