{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T07:01:53Z","timestamp":1761894113406},"reference-count":45,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and \u03b2-cell dysfunction. Islet amyloid is associated with reduced \u03b2-cell mass and function and develops in the majority of our C57BL\/6J \u00d7 DBA\/2J (F<jats:sub>1<\/jats:sub>) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL\/6J (BL6) and DBA\/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL\/6J \u00d7 DBA\/2J F<jats:sub>1<\/jats:sub>mice ( n = 17) on a 9% (wt\/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F<jats:sub>1<\/jats:sub>: 76%, DBA2: 100%). However, the prevalence (%amyloid-positive islets; BL6: 14 \u00b1 3%, F<jats:sub>1<\/jats:sub>: 44 \u00b1 8%, DBA2: 49 \u00b1 9%, P &lt; 0.05) and severity (%islet area occupied by amyloid; BL6: 0.03 \u00b1 0.01%, F<jats:sub>1<\/jats:sub>: 9.2 \u00b1 2.9%, DBA2: 5.7 \u00b1 2.3%, p \u2264 0.01) were significantly lower in BL6 than F<jats:sub>1<\/jats:sub>and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F<jats:sub>1<\/jats:sub>( r<jats:sup>2<\/jats:sup>= 0.75, P &lt; 0.001) and DBA2 ( r<jats:sup>2<\/jats:sup>= 0.87, P &lt; 0.001) mice but not BL6 mice ( r<jats:sup>2<\/jats:sup>= 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA\/2J genes (F<jats:sub>1<\/jats:sub>and DBA2 mice) being more susceptible to amyloid deposition that replaces \u03b2-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease.<\/jats:p>","DOI":"10.1152\/ajpendo.00471.2004","type":"journal-article","created":{"date-parts":[[2005,5,18]],"date-time":"2005-05-18T03:14:33Z","timestamp":1116386073000},"page":"E703-E709","source":"Crossref","is-referenced-by-count":12,"title":["Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice"],"prefix":"10.1152","volume":"289","author":[{"given":"Rebecca L.","family":"Hull","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissah R.","family":"Watts","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichi","family":"Kodama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-ping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina M.","family":"Utzschneider","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darcy B.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Vidal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Kahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201x.2001.00794.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.49.12.2056"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.1.133"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.23.4.465"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"R6","unstructured":"Clark A, Wells CA, Buley ID, Cruickshank JK, Vanhegan RI, Matthews DR, Cooper GJS, Holman RR, and Turner RC.Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type-2 diabetes.Diabetes Res Clin Exp9: 151\u2013159, 1988."},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1007\/BF01221856"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.23.8628"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.12.1457"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Elbein SC, Hasstedt SJ, Wegner K, and Kahn SE.Heritability of pancreatic beta-cell function among nondiabetic members of Caucasian familial type 2 diabetic kindreds.J Clin Endocrinol Metab84: 1398\u20131403, 1999.","DOI":"10.1210\/jc.84.4.1398"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra002168"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(93)81444-5"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1400"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0219"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.213"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051175"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1007\/BF00400803"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.372"},{"key":"R19","unstructured":"Hull RL, Kodama K, Utzschneider KM, Carr DB, Prigeon RL, and Kahn SE.Dietary-fat-induced obesity in mice results in beta cell hyperplasia but not increased insulin release: evidence for specificity of impaired beta cell adaptation.Diabetologia. 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