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Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus
Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386890/ https://www.ncbi.nlm.nih.gov/pubmed/18497871 http://dx.doi.org/10.1155/2008/697035 |
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author | Höppener, J. W. M. Jacobs, H. M. Wierup, N. Sotthewes, G. Sprong, M. de Vos, P. Berger, R. Sundler, F. Ahrén, B. |
author_facet | Höppener, J. W. M. Jacobs, H. M. Wierup, N. Sotthewes, G. Sprong, M. de Vos, P. Berger, R. Sundler, F. Ahrén, B. |
author_sort | Höppener, J. W. M. |
collection | PubMed |
description | Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process. |
format | Text |
id | pubmed-2386890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-23868902008-05-22 Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus Höppener, J. W. M. Jacobs, H. M. Wierup, N. Sotthewes, G. Sprong, M. de Vos, P. Berger, R. Sundler, F. Ahrén, B. Exp Diabetes Res Research Article Human islet amyloid polypeptide (hIAPP), a pancreatic islet protein of 37 amino acids, is the main component of islet amyloid, seen at autopsy in patients with type 2 diabetes mellitus (DM2). To investigate the roles of hIAPP and islet amyloid in DM2, we generated transgenic mice expressing hIAPP in their islet beta cells. In this study, we found that after a long-term, high-fat diet challenge islet amyloid was observed in only 4 of 19 hIAPP transgenic mice. hIAPP transgenic females exhibited severe glucose intolerance, which was associated with a downregulation of GLUT-2 mRNA expression. In isolated islets from hIAPP males cultured for 3 weeks on high-glucose medium, the percentage of amyloid containing islets increased from 5.5% to 70%. This ex vivo system will allow a more rapid, convenient, and specific study of factors influencing islet amyloidosis as well as of therapeutic strategies to interfere with this pathological process. Hindawi Publishing Corporation 2008 2008-05-12 /pmc/articles/PMC2386890/ /pubmed/18497871 http://dx.doi.org/10.1155/2008/697035 Text en Copyright © 2008 J. W. M. Höppener et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Höppener, J. W. M. Jacobs, H. M. Wierup, N. Sotthewes, G. Sprong, M. de Vos, P. Berger, R. Sundler, F. Ahrén, B. Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title | Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title_full | Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title_fullStr | Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title_full_unstemmed | Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title_short | Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus |
title_sort | human islet amyloid polypeptide transgenic mice: in vivo and ex vivo models for the role of hiapp in type 2 diabetes mellitus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386890/ https://www.ncbi.nlm.nih.gov/pubmed/18497871 http://dx.doi.org/10.1155/2008/697035 |
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