{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:11:35Z","timestamp":1767849095087,"version":"3.49.0"},"reference-count":39,"publisher":"American Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":4349,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,1,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>Aggregation of human amylin\/islet amyloid polypeptide (hA\/hIAPP) into small soluble \u03b2-sheet\u2013containing oligomers is linked to islet \u03b2-cell degeneration and the pathogenesis of type 2 diabetes. Here, we used tetracycline, which modifies hA\/hIAPP oligomerization, to probe mechanisms whereby hA\/hIAPP causes diabetes in hemizygous hA\/hIAPP-transgenic mice.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>We chronically treated hemizygous hA\/hIAPP transgenic mice with oral tetracycline to determine its effects on rates of diabetes initiation, progression, and survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Homozygous mice developed severe spontaneous diabetes due to islet \u03b2-cell loss. Hemizygous transgenic animals also developed spontaneous diabetes, although severity was less and progression rates slower. Pathogenesis was characterized by initial islet \u03b2-cell dysfunction followed by progressive \u03b2-cell loss. Islet amyloid was absent from hemizygous animals with early-onset diabetes and correlated positively with longevity. Some long-lived nondiabetic hemizygous animals also had large islet-amyloid areas, showing that amyloid itself was not intrinsically cytotoxic. Administration of tetracycline dose-dependently ameliorated hyperglycemia and polydipsia, delayed rates of diabetes initiation and progression, and increased longevity compared with water-treated controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This is the first report to show that treating hA\/hIAPP transgenic mice with a modifier of hA\/hIAPP misfolding can ameliorate their diabetic phenotype. Fibrillar amyloid was neither necessary nor sufficient to cause diabetes and indeed was positively correlated with longevity therein, whereas early- to mid-stage diabetes was associated with islet \u03b2-cell dysfunction followed by \u03b2-cell loss. Interventions capable of suppressing misfolding in soluble hA\/hIAPP oligomers rather than mature fibrils may have potential for treating or preventing type 2 diabetes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/db09-0548","type":"journal-article","created":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T02:34:55Z","timestamp":1254364495000},"page":"161-171","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":44,"title":["Tetracycline Treatment Retards the Onset and Slows the Progression of Diabetes in Human Amylin\/Islet Amyloid Polypeptide Transgenic Mice"],"prefix":"10.2337","volume":"59","author":[{"given":"Jacqueline F.","family":"Aitken","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, Faculty of Science, University of Auckland, Auckland, New Zealand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry M.","family":"Loomes","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, Faculty of Science, University of Auckland, Auckland, New Zealand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David W.","family":"Scott","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;"},{"name":"Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivanand","family":"Reddy","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Medical and Health 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