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Islet amyloid development in a mouse strain lacking endogenous islet amyloid polypeptide (IAPP) but expressing human IAPP
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
Linkoping Univ, Dept Biomed & Surg, Div Med Cell Biol, Linkoping, Sweden Univ Lund, Dept Physiol Sci, Div Mol & Cellular Physiol, S-22100 Lund, Sweden Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden Univ Chicago, Dept Biochem, Chicago, IL 60637 USA Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
Linkoping Univ, Dept Biomed & Surg, Div Med Cell Biol, Linkoping, Sweden Univ Lund, Dept Physiol Sci, Div Mol & Cellular Physiol, S-22100 Lund, Sweden Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden Univ Chicago, Dept Biochem, Chicago, IL 60637 USA Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
Linkoping Univ, Dept Biomed & Surg, Div Med Cell Biol, Linkoping, Sweden Univ Lund, Dept Physiol Sci, Div Mol & Cellular Physiol, S-22100 Lund, Sweden Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden Univ Chicago, Dept Biochem, Chicago, IL 60637 USA Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA.
2000 (English)In: Molecular medicine (Cambridge, Mass. Print), ISSN 1076-1551, E-ISSN 1528-3658, Vol. 6, no 12, 998-1007 p.Article in journal (Refereed) Published
Abstract [en]

Background: Several mouse strains expressing human islet amyloid polypeptide (IAPP) have been created to study development of islet amyloid and its impact on islet cell function. The tendency to form islet amyloid has varied strongly among these strains by factors that have not been elucidated. Because some beta cell granule components are known to inhibit IAPP fibril formation in vitro, we wanted to determine whether a mouse strain expressing human IAPP but lacking the nonamyloidogenic mouse IAPP is more prone to develop islet amyloidosis. Materials and Methods: Such a strain was created by cross-breeding a transgenic mouse strain and an IAPP null mouse strain. Results: when fed a fat-enriched diet, male mice expressing only human IAPP developed islet amyloid earlier and to a higher extent than did mice expressing both human and mouse IAPP. Supporting these results, we found that mouse IAPP dose-dependently inhibits formation of fibrils from human IAPP. Conclusions: Female mice did not develop amyloid deposits, although small extracellular amorphous IAPP deposits were found in some islets. When cultivated in vitro, amyloid deposits occurred within 10 days in islets from either male or female mice expressing only human IAPP. The study shows that formation of islet amyloid may be dependent on the environment, including the presence or absence of fibril inhibitors or promoters.

Place, publisher, year, edition, pages
2000. Vol. 6, no 12, 998-1007 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-49414OAI: oai:DiVA.org:liu-49414DiVA: diva2:270310
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12

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