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For the species that develop type 2 diabetes, their IAPP is cytotoxic, and a \u03b2-sheet at G24 is observed during the lag phase prior to fibril formation. In contrast, the species that do not develop type 2 diabetes have nontoxic IAPP, and their IAPP does not form this \u03b2-sheet structure. Pig IAPP forms oligomers, but with a different structure that is nontoxic. Thus, an oligomer with a parallel \u03b2-sheet at G24 that resembles that of the known human IAPP oligomer correlates with cytotoxicity and propensity for type 2 diabetes. These results indicate that the sequence within the 20 to 29 region of human islet amyloid polypeptide (hIAPP), long known to correlate with type 2 diabetes in mammals, determines the structure and toxicity of an oligomer, supporting the oligomer hypothesis for type 2 diabetes and providing an explanation other than plaque formation for why some mammals develop insulin deficiency in late-stage type 2 diabetes, and others do not.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2530570123","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T20:01:11Z","timestamp":1769457671000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":6,"title":["Mammals that can develop type 2 diabetes have a similarly structured \u03b2-sheet amyloid oligomer"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9910-6953","authenticated-orcid":false,"given":"Brynn E.","family":"LeMasters","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlyn R.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-3683","authenticated-orcid":false,"given":"Justin P.","family":"Lomont","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Chalyavi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kacie L.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald S.","family":"Stapleton","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney S.","family":"Dicke","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan D.","family":"Attie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin T.","family":"Zanni","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Wisconsin-Madison","place":["Madison"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"e_1_3_4_1_2","unstructured":"CDC National Diabetes Statistics Report 2020: Estimates of diabetes and its burden in the United States (Rep. 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