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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

Hoppener, J. W. M.; Jacobs, H. M.; Wierup, N.; Sotthewes, G.; Sprong, M.; de Vos, P.; Berger, R.; Sundler, Frank LU and Ahrén, Bo LU (2008) In Experimental Diabetes Research
Abstract
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%.... (More)
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. Copyright (C) 2008 J. W. M. Hoppener et al. (Less)
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publishing date
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Contribution to journal
publication status
published
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in
Experimental Diabetes Research
publisher
Hindawi Publishing Corporation
external identifiers
  • wos:000267194700001
  • scopus:44649119876
ISSN
1687-5214
DOI
10.1155/2008/697035
language
English
LU publication?
yes
id
cf737454-377c-4275-a323-9699dbe4bda8 (old id 1440493)
date added to LUP
2009-07-27 11:52:52
date last changed
2017-11-12 03:23:51
@article{cf737454-377c-4275-a323-9699dbe4bda8,
  abstract     = {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. Copyright (C) 2008 J. W. M. Hoppener et al.},
  articleno    = {697035},
  author       = {Hoppener, J. W. M. and Jacobs, H. M. and Wierup, N. and Sotthewes, G. and Sprong, M. and de Vos, P. and Berger, R. and Sundler, Frank and Ahrén, Bo},
  issn         = {1687-5214},
  language     = {eng},
  publisher    = {Hindawi Publishing Corporation},
  series       = {Experimental Diabetes Research},
  title        = {Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus},
  url          = {http://dx.doi.org/10.1155/2008/697035},
  year         = {2008},
}