PMID- 29155303 OWN - NLM STAT- MEDLINE DCOM- 20180108 LR - 20180108 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 192 DP - 2018 Jan 1 TI - Therapeutic vaccine against IL-1beta improved glucose control in a mouse model of type 2 diabetes. PG - 68-74 LID - S0024-3205(17)30599-4 [pii] LID - 10.1016/j.lfs.2017.11.021 [doi] AB - AIMS: Inflammation is strongly associated with the mechanism of beta-cell failure in type 2 diabetes mellitus (T2DM). Blockade of the key proinflammatory cytokine IL-1beta has been implicated as a promising therapeutic strategy for the prevention and treatment of type 2 diabetes. In this study, we developed an IL-1beta-targeted therapeutic vaccine consisting of an IL-1beta epitope peptide (A1beta) and assessed its efficacy on a diabetic KK-A(y) mouse model. MAIN METHODS: KK-A(y) mice were immunized with A1beta for three injections at a 2-week interval. The induced antibody titers, body weights and blood glucose levels were monitored every two weeks. Then the intraperitoneal glucose tolerance test and insulin tolerance test were performed. The beta-cell mass, beta-cell apoptosis and proliferation were evaluated by immunofluorescence. IL-1beta gene expression in islets was also measured by quantitative RT-PCR. KEY FINDINGS: A1beta immunization induced robust antibody responses, reduced body weight gain, improved glucose tolerance and insulin sensitivity in KK-A(y) mice. Moreover, A1beta restored beta-cell mass, inhibited beta-cell apoptosis, enhanced beta-cell proliferation and downregulated IL-1beta expression. SIGNIFICANCE: The novel IL-1beta-targeted epitope vaccine has the therapeutic potential for T2DM. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Zhang, Yue AU - Zhang Y AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. FAU - Yu, Xiao-Lin AU - Yu XL AD - State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. FAU - Zha, Jun AU - Zha J AD - State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. FAU - Mao, Li-Zhen AU - Mao LZ AD - Asialand Biomed Technology Co., Ltd., Changzhou, China. FAU - Chai, Jia-Qian AU - Chai JQ AD - Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Agricultural University, Taian, Shandong, China. Electronic address: jqchai@sdau.edu.cn. FAU - Liu, Rui-Tian AU - Liu RT AD - State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, China. Electronic address: rtliu@ipe.ac.cn. LA - eng PT - Journal Article DEP - 20171116 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Antibodies) RN - 0 (Blood Glucose) RN - 0 (Epitopes) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-1beta) RN - 0 (Vaccines) SB - IM MH - Animals MH - Antibodies/analysis MH - Apoptosis MH - Blood Glucose/*metabolism MH - Body Weight MH - Cell Proliferation MH - Diabetes Mellitus, Type 2/genetics/*metabolism/*therapy MH - Disease Models, Animal MH - Down-Regulation/genetics/immunology MH - Epitopes/immunology MH - Glucose Tolerance Test MH - Immunoglobulin G/analysis/biosynthesis MH - Insulin Resistance MH - Insulin-Secreting Cells/metabolism MH - Interleukin-1beta/*immunology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Vaccines/immunology/*therapeutic use OTO - NOTNLM OT - IL-1beta OT - Islet inflammation OT - Therapeutic vaccine OT - Type 2 diabetes EDAT- 2017/11/21 06:00 MHDA- 2018/01/09 06:00 CRDT- 2017/11/21 06:00 PHST- 2017/09/05 00:00 [received] PHST- 2017/11/03 00:00 [revised] PHST- 2017/11/15 00:00 [accepted] PHST- 2017/11/21 06:00 [pubmed] PHST- 2018/01/09 06:00 [medline] PHST- 2017/11/21 06:00 [entrez] AID - S0024-3205(17)30599-4 [pii] AID - 10.1016/j.lfs.2017.11.021 [doi] PST - ppublish SO - Life Sci. 2018 Jan 1;192:68-74. doi: 10.1016/j.lfs.2017.11.021. Epub 2017 Nov 16.