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  3. Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus.
 

Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus.

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BORIS DOI
10.7892/boris.146997
Date of Publication
March 2, 2020
Publication Type
Article
Division/Institute

Department for BioMed...

Department for BioMed...

Universitätsklinik fü...

Institut für Anatomie...

Contributor
Rösti, Elisa Simona
Department for BioMedical Research, Forschungsgruppe Rheumatologie
Universitätsklinik für Rheumatologie, Immunologie und Allergologie
Universitätsklinik für Rheumatologie, Immunologie und Allergologie, Fachbereich Immunologie
Boyle, Christina N
Zeman, Daniel T
Sande Melon, Marcos
Institut für Anatomie
Storni, Federico Lorenzo
Department for BioMedical Research, Forschungsgruppe Rheumatologie
Universitätsklinik für Viszerale Chirurgie und Medizin, Viszeral- und Transplantationschirurgie
Cabral de Miranda, Gustavo
Universitätsklinik für Rheumatologie, Immunologie und Allergologie
Knuth, Alexander
Lutz, Thomas A
Vogel, Monique
Department for BioMedical Research (DBMR)
Universitätsklinik für Rheumatologie, Immunologie und Allergologie
Bachmann, Martin
Universitätsklinik für Rheumatologie, Immunologie und Allergologie
Department for BioMedical Research, Forschungsgruppe Rheumatologie
Subject(s)

600 - Technology::610...

Series
Vaccines
ISSN or ISBN (if monograph)
2076-393X
Publisher
MDPI
Language
English
Publisher DOI
10.3390/vaccines8010116
PubMed ID
32131431
Uncontrolled Keywords

T2DM amyloid islet am...

Description
Type 2 diabetes mellitus (T2DM) is a chronic progressive disease characterized by insulin resistance and insufficient insulin secretion to maintain normoglycemia. The majority of T2DM patients bear amyloid deposits mainly composed of islet amyloid polypeptide (IAPP) in their pancreatic islets. These-originally β-cell secretory products-extracellular aggregates are cytotoxic for insulin-producing β-cells and are associated with β-cell loss and inflammation in T2DM advanced stages. Due to the absence of T2DM preventive medicaments and the presence of only symptomatic drugs acting towards increasing hormone secretion and action, we aimed at establishing a novel disease-modifying therapy targeting the cytotoxic IAPP deposits in order to prevent the development of T2DM. We generated a vaccine based on virus-like particles (VLPs), devoid of genomic material, coupled to IAPP peptides inducing specific antibodies against aggregated, but not monomeric IAPP. Using a mouse model of islet amyloidosis, we demonstrate in vivo that our vaccine induced a potent antibody response against aggregated, but not soluble IAPP, strikingly preventing IAPP depositions, delaying onset of hyperglycemia and the induction of the associated pro-inflammatory cytokine Interleukin 1β (IL-1β). We offer the first cost-effective and safe disease-modifying approach targeting islet dysfunction in T2DM, preventing pathogenic aggregates without disturbing physiological IAPP function.
Handle
https://boris-portal.unibe.ch/handle/20.500.12422/55425
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File(s)
FileFile TypeFormatSizeLicensePublisher/Copright statementContent
Vaccination against amyloidogenic.pdftextAdobe PDF16.13 MBAttribution (CC BY 4.0)publishedOpen
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