{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:36:15Z","timestamp":1792571775381,"version":"4.5.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"7","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,7,1]]},"abstract":"<jats:p>Islet amyloid deposition in type 2 diabetes is associated with reduced \u03b2-cell mass. Therefore, interventions aimed at reducing islet amyloid formation may help preserve \u03b2-cell mass in type 2 diabetes. Rosiglitazone and metformin act by different mechanisms to improve insulin sensitivity and thereby reduce \u03b2-cell secretory demand, resulting in decreased release of insulin and islet amyloid polypeptide (IAPP), the unique constituent of islet amyloid deposits. We hypothesized that this reduced \u03b2-cell secretory demand would lead to reduced islet amyloid formation. Human IAPP (hIAPP) transgenic mice, a model of islet amyloid, were treated for 12 months with rosiglitazone (1.5 mg \u00b7 kg\u22121 \u00b7 day\u22121, n = 19), metformin (1 g \u00b7 kg\u22121 \u00b7 day\u22121, n = 18), or control (n = 17). At the end of the study, islet amyloid prevalence (percent islets containing amyloid) and severity (percent islet area occupied by amyloid), islet mass, \u03b2-cell mass, and insulin release were determined. Islet amyloid prevalence (44 \u00b1 8, 13 \u00b1 4, and 11 \u00b1 3% for control, metformin-, and rosiglitazone-treated mice, respectively) and severity (9.2 \u00b1 3.0, 0.22 \u00b1 0.11, and 0.10 \u00b1 0.05% for control, metformin-, and rosiglitazone-treated mice, respectively) were markedly reduced with both rosiglitazone (P &amp;lt; 0.001 for both measures) and metformin treatment (P &amp;lt; 0.001 for both measures). Both treatments were associated with reduced insulin release assessed as the acute insulin response to intravenous glucose (2,189 \u00b1 857, 621 \u00b1 256, and 14 \u00b1 158 pmol\/l for control, metformin-, and rosiglitazone-treated mice, respectively; P &amp;lt; 0.05 for metformin vs. control and P &amp;lt; 0.005 for rosiglitazone vs. control), consistent with reduced secretory demand. Similarly, islet mass (33.4 \u00b1 7.0, 16.6 \u00b1 3.6, and 12.2 \u00b1 2.1 mg for control, metformin-, and rosiglitazone-treated mice, respectively) was not different with metformin treatment (P = 0.06 vs. control) but was significantly lower with rosiglitazone treatment (P &amp;lt; 0.05 vs. control). When the decreased islet mass was accounted for, the islet amyloid\u2013related decrease in \u03b2-cell mass (percent \u03b2-cell mass\/islet mass) was ameliorated in both rosiglitazone- and metformin-treated animals (57.9 \u00b1 3.1, 64.7 \u00b1 1.4, and 66.1 \u00b1 1.6% for control, metformin-, and rosiglitazone-treated mice, respectively; P &amp;lt; 0.05 for metformin or rosiglitazone vs. control). In summary, rosiglitazone and metformin protect \u03b2-cells from the deleterious effects of islet amyloid, and this effect may contribute to the ability of these treatments to alleviate the progressive loss of \u03b2-cell mass and function in type 2 diabetes.<\/jats:p>","DOI":"10.2337\/diabetes.54.7.2235","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2235-2244","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":85,"title":["Long-Term Treatment With Rosiglitazone and Metformin Reduces the Extent of, but Does Not Prevent, Islet Amyloid Deposition in Mice Expressing the Gene for Human Islet Amyloid Polypeptide"],"prefix":"10.2337","volume":"54","author":[{"given":"Rebecca L.","family":"Hull","sequence":"first","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Ping","family":"Shen","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissah R.","family":"Watts","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Kodama","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy B.","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina M.","family":"Utzschneider","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakeneh","family":"Zraika","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208120147700_R1","doi-asserted-by":"crossref","unstructured":"Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz PU: Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. 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