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Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo
BACKGROUND: The fibrillation of islet amyloid polypeptide (IAPP) triggered the amyloid deposition, then enhanced the loss of the pancreatic islet mass. However, it is not clear what factor is the determinant in development of the fibril formation. The aim of this study is to investigate the effects...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845206/ https://www.ncbi.nlm.nih.gov/pubmed/29523142 http://dx.doi.org/10.1186/s12944-018-0694-8 |
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author | Mo, Xiao-Dan Gao, Li-Ping Wang, Qing-Jun Yin, Jie Jing, Yu-Hong |
author_facet | Mo, Xiao-Dan Gao, Li-Ping Wang, Qing-Jun Yin, Jie Jing, Yu-Hong |
author_sort | Mo, Xiao-Dan |
collection | PubMed |
description | BACKGROUND: The fibrillation of islet amyloid polypeptide (IAPP) triggered the amyloid deposition, then enhanced the loss of the pancreatic islet mass. However, it is not clear what factor is the determinant in development of the fibril formation. The aim of this study is to investigate the effects of lipid on IAPP fibril and its injury on pancreatic islet. METHODS: The fibril form of human IAPP (hIAPP) was tested using thioflavin-T fluorescence assay and transmission electron microscope technology after incubated with palmitate for 5 h at 25 °C. The cytotoxicity of fibril hIAPP was evaluated in INS-1 cells through analyzing the leakage of cell membrane and cell apoptosis. Type 2 diabetes mellitus (T2DM) animal model was induced with low dose streptozotocin combined the high-fat diet feeding for two months in rats. Plasma biochemistry parameters were measured before sacrificed. Pancreatic islet was isolated to evaluate their function. RESULTS: The results showed that co-incubation of hIAPP and palmitate induced more fibril form. Fibril hIAPP induced cell lesions including cell membrane leakage and cell apoptosis accompanied insulin mRNA decrease in INS-1 cell lines. In vivo, Plasma glucose, triglyceride, rIAPP and insulin increased in T2DM rats compared with the control group. In addition, IAPP and insulin mRNA increased in pancreatic islet of T2DM rats. Furthermore, T2DM induced the reduction of insulin receptor expression and cleaved caspase-3 overexpression in pancreatic islet. CONCLUSIONS: Results in vivo and in vitro suggested that lipid and IAPP plays a synergistic effect on pancreatic islet cell damage, which implicated in enhancing the IAPP expression and accelerating the fibril formation of IAPP. |
format | Online Article Text |
id | pubmed-5845206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58452062018-03-19 Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo Mo, Xiao-Dan Gao, Li-Ping Wang, Qing-Jun Yin, Jie Jing, Yu-Hong Lipids Health Dis Research BACKGROUND: The fibrillation of islet amyloid polypeptide (IAPP) triggered the amyloid deposition, then enhanced the loss of the pancreatic islet mass. However, it is not clear what factor is the determinant in development of the fibril formation. The aim of this study is to investigate the effects of lipid on IAPP fibril and its injury on pancreatic islet. METHODS: The fibril form of human IAPP (hIAPP) was tested using thioflavin-T fluorescence assay and transmission electron microscope technology after incubated with palmitate for 5 h at 25 °C. The cytotoxicity of fibril hIAPP was evaluated in INS-1 cells through analyzing the leakage of cell membrane and cell apoptosis. Type 2 diabetes mellitus (T2DM) animal model was induced with low dose streptozotocin combined the high-fat diet feeding for two months in rats. Plasma biochemistry parameters were measured before sacrificed. Pancreatic islet was isolated to evaluate their function. RESULTS: The results showed that co-incubation of hIAPP and palmitate induced more fibril form. Fibril hIAPP induced cell lesions including cell membrane leakage and cell apoptosis accompanied insulin mRNA decrease in INS-1 cell lines. In vivo, Plasma glucose, triglyceride, rIAPP and insulin increased in T2DM rats compared with the control group. In addition, IAPP and insulin mRNA increased in pancreatic islet of T2DM rats. Furthermore, T2DM induced the reduction of insulin receptor expression and cleaved caspase-3 overexpression in pancreatic islet. CONCLUSIONS: Results in vivo and in vitro suggested that lipid and IAPP plays a synergistic effect on pancreatic islet cell damage, which implicated in enhancing the IAPP expression and accelerating the fibril formation of IAPP. BioMed Central 2018-03-09 /pmc/articles/PMC5845206/ /pubmed/29523142 http://dx.doi.org/10.1186/s12944-018-0694-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Mo, Xiao-Dan Gao, Li-Ping Wang, Qing-Jun Yin, Jie Jing, Yu-Hong Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title | Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title_full | Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title_fullStr | Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title_full_unstemmed | Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title_short | Lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
title_sort | lipid accelerating the fibril of islet amyloid polypeptide aggravated the pancreatic islet injury in vitro and in vivo |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845206/ https://www.ncbi.nlm.nih.gov/pubmed/29523142 http://dx.doi.org/10.1186/s12944-018-0694-8 |
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