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Experimental Diabetes Research
Volume 2008, Article ID 697035, 8 pages
http://dx.doi.org/10.1155/2008/697035
Research Article

Human Islet Amyloid Polypeptide Transgenic Mice: In Vivo and Ex Vivo Models for the Role of hIAPP in Type 2 Diabetes Mellitus

1Division of Biomedical Genetics, Department of Metabolic and Endocrine Diseases, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
2Netherlands Metabolomics Centre, location Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
3Division Laboratories and Pharmacy, Department of Endocrinology, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands
4Department of Experimental Medical Sciences, Lund University, BMC, C 12, S-221 84 Lund, Sweden
5Division of Medical Biology, Department of Pathology and Laboratory Medicine, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands
6Department of Clinical Sciences, Lund University, BMC, C 12, S-221 84 Lund, Sweden

Received 9 October 2007; Revised 30 January 2008; Accepted 14 February 2008

Academic Editor: Hiroshi Okamoto

Copyright © 2008 J. W. M. Höppener et al. 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.

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.