{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:41:54Z","timestamp":1788914514011,"version":"build-2803163510"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"7","license":[{"start":{"date-parts":[[2015,5,16]],"date-time":"2015-05-16T00:00:00Z","timestamp":1431734400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,7,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The loss of \u03b2-cell function and \u03b2-cell death are key features of diabetes. A range of mechanisms are thought to contribute to \u03b2-cell loss, including islet amyloid formation by the neuropancreatic hormone amylin (islet amyloid polypeptide, IAPP). Islet amyloid deposition also contributes to the failure of islet transplants. There are no therapeutic strategies for the treatment or prevention of islet amyloidosis. Aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen, at clinically relevant doses, have been proposed to inhibit amyloid formation by amylin and thus may hold promise for treatment of islet amyloidosis. These compounds are potentially attractive given the importance of inflammation in islet amyloidosis and given the fact that there are no anti-islet amyloid agents in the clinic. We show that aspirin, even in 20-fold excess, has no effect on the kinetics of amyloid formation by amylin as judged by thioflavin-T binding, right angle light scattering, and transmission electron microscopy, nor does it alter the morphology of resulting amyloid fibrils. Aspirin showed no ability to disaggregate preformed amylin amyloid fibrils under the conditions of these studies, 25 \u00b0C and pH 7.4. Ketoprofen is similarly ineffective at inhibiting amylin amyloid formation. The compounds do, however, interfere with circular dichroism- and Congo Red-based assays of amylin amyloid formation. This study highlights the importance of using multiple methods to follow amyloid formation when screening inhibitors.<\/jats:p>","DOI":"10.1021\/cb500162w","type":"journal-article","created":{"date-parts":[[2014,5,16]],"date-time":"2014-05-16T09:55:17Z","timestamp":1400234117000},"page":"1632-1637","source":"Crossref","is-referenced-by-count":11,"title":["Aspirin, Diabetes, and Amyloid: Re-examination of\nthe Inhibition of Amyloid Formation by Aspirin and Ketoprofen"],"prefix":"10.1021","volume":"9","author":[{"given":"Ling-Hsien","family":"Tu","sequence":"first","affiliation":[{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794-3400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Noor","sequence":"additional","affiliation":[{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794-3400"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Cao","sequence":"additional","affiliation":[{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794-3400"]},{"name":"New York University School of Medicine , , , ,","place":["New York, New York, United States, 10016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Raleigh","sequence":"additional","affiliation":[{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794-3400"]},{"name":"Stony Brook University , , , ,","place":["Stony Brook, New York, United States, 11794-3400"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,5,16]]},"reference":[{"key":"2026090316302950600_cit1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.cell.2012.02.010","article-title":"Diabetes mellitus and the beta cell: The last ten years","volume":"148","author":"Ashcroft","year":"2012","journal-title":"Cell"},{"key":"2026090316302950600_cit2","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nri2925","article-title":"Type 2 diabetes\nas an inflammatory disease","volume":"11","author":"Donath","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2026090316302950600_cit3","first-page":"151","article-title":"Islet amyloid, increased alpha-cells,\nreduced beta-cells\nand exocrine fibrosis-quantitative changes in the pancreas in type\n2 diabetes","volume":"9","author":"Clark","year":"1988","journal-title":"Diabetes Res."},{"key":"2026090316302950600_cit4","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1038\/368756a0","article-title":"Pancreatic-islet\ncell toxicity of amylin associated with type-2 diabetes-mellitus","volume":"368","author":"Lorenzo","year":"1994","journal-title":"Nature"},{"key":"2026090316302950600_cit5","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1111\/j.1742-4658.2006.05367.x","article-title":"The\naggregation potential of human amylin determines its cytotoxicity\ntowards islet beta-cells","volume":"273","author":"Konarkowska","year":"2006","journal-title":"FEBS. J."},{"key":"2026090316302950600_cit6","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJMc0802893","article-title":"Widespread amyloid\ndeposition in transplanted human pancreatic islets","volume":"359","author":"Westermark","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"2026090316302950600_cit7","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1073\/pnas.0909024107","article-title":"Islet amyloid deposition\nlimits the viability of human islet grafts but not porcine islet grafts","volume":"107","author":"Potter","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090316302950600_cit8","doi-asserted-by":"crossref","first-page":"634","DOI":"10.2337\/diab.39.5.634","article-title":"Evidence of cosecretion of islet\namyloid polypeptide and insulin by beta-cells","volume":"39","author":"Kahn","year":"1990","journal-title":"Diabetes"},{"key":"2026090316302950600_cit9","doi-asserted-by":"crossref","first-page":"784","DOI":"10.2337\/diacare.26.3.784","article-title":"Pramlintide\nas an adjunct to insulin therapy improves long-term glycemic and weight\ncontrol in patients with type 2 diabetes \u2013 A 1-year randomized\ncontrolled trial","volume":"26","author":"Hollander","year":"2003","journal-title":"Diabetes Care"},{"key":"2026090316302950600_cit10","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1021\/bi2015162","article-title":"Analysis of the\ninhibition and remodeling of islet\namyloid polypeptide amyloid fibers by flavanols","volume":"51","author":"Cao","year":"2012","journal-title":"Biochemistry"},{"key":"2026090316302950600_cit11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.jmb.2010.12.028","article-title":"Inhibition of glycosaminoglycan-mediated\namyloid formation\nby islet amyloid polypeptide and proIAPP processing intermediates","volume":"406","author":"Meng","year":"2011","journal-title":"J. Mol. Biol."},{"key":"2026090316302950600_cit12","doi-asserted-by":"crossref","first-page":"14454","DOI":"10.1021\/bi048582a","article-title":"Inhibition of islet\namyloid polypeptide fibril formation: A potential role for heteroaromatic\ninteractions","volume":"43","author":"Porat","year":"2004","journal-title":"Biochemistry"},{"key":"2026090316302950600_cit13","doi-asserted-by":"crossref","first-page":"14340","DOI":"10.1021\/ja1046186","article-title":"Combination of kinetically\nselected\ninhibitors in Trans leads to highly effective inhibition of amyloid\nformation","volume":"132","author":"Meng","year":"2010","journal-title":"J. Am. Chem. 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Biol."},{"key":"2026090316302950600_cit16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/j.1747-0285.2005.00318.x","article-title":"Inhibition of amyloid fibril formation\nby polyphenols: structural similarity and aromatic interactions as\na common inhibition mechanism","volume":"67","author":"Porat","year":"2006","journal-title":"Chem. Biol. Drug\nDes."},{"key":"2026090316302950600_cit17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/pro.2023","article-title":"Morin hydrate\ninhibits amyloid formation by islet amyloid\npolypeptide and disaggregates amyloid fibers","volume":"21","author":"Noor","year":"2012","journal-title":"Protien Sci."},{"key":"2026090316302950600_cit18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1055\/s-2003-37493","article-title":"Aspirin and\ndiabetes: Inhibition\nof amylin aggregation by nonsteroidal anti-inflammatory drugs","volume":"111","author":"Thomas","year":"2003","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"2026090316302950600_cit19","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.2337\/db06-1650","article-title":"Increased number of islet-associated\nmacrophages in type 2 diabetes","volume":"56","author":"Ehses","year":"2007","journal-title":"Diabetes"},{"key":"2026090316302950600_cit20","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nri2925","article-title":"Type 2 diabetes\nas an inflammatory disease","volume":"11","author":"Donath","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2026090316302950600_cit21","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/ni.1935","article-title":"Activation\nof the NLRP3 inflammasome by islet amyloid\npolypeptide provides a mechanism for enhanced IL-1\u03b2 in type\n2 diabetes","volume":"11","author":"Masters","year":"2010","journal-title":"Nat. Immunol."},{"key":"2026090316302950600_cit22","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.2337\/db13-0863","article-title":"Resident macrophages\nmediate islet\namyloid polypeptide-induced islet IL-1\u03b2 production and \u03b2-cell\ndysfunction","volume":"63","author":"Westwell-Roper","year":"2014","journal-title":"Diabetes"},{"key":"2026090316302950600_cit23","first-page":"36","article-title":"Use of salsalate\nto target inflammation in the treatment\nof insulin resistance and type 2 diabetes","volume":"1","author":"Goldfine","year":"2008","journal-title":"CTS:\nClin. Transl. Sci."},{"key":"2026090316302950600_cit24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.tem.2013.01.007","article-title":"Islet inflammation:\na unifying target for diabetes treatment?","volume":"24","author":"Imai","year":"2013","journal-title":"Trends\nEndocrinol. Metab."},{"key":"2026090316302950600_cit25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/13506129509031881","article-title":"Thioflavine-T\ninteraction with amyloid beta-sheet structures","volume":"2","author":"Levine","year":"1995","journal-title":"Amyloid"},{"key":"2026090316302950600_cit26","doi-asserted-by":"crossref","first-page":"6016","DOI":"10.1021\/bi702518m","article-title":"Rifampicin\ndoes not prevent amyloid fibril formation by human islet amyloid polypeptide\nbut does inhibit fibril thioflavin-T interactions: Implications for\nmechanistic studies beta-cell death","volume":"47","author":"Meng","year":"2008","journal-title":"Biochemistry"},{"key":"2026090316302950600_cit27","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1002\/cbic.200800052","article-title":"The fluorescent\namino acid p-cyanophenylalanine provides an intrinsic\nprobe of amyloid\nformation","volume":"9","author":"Marek","year":"2008","journal-title":"ChemBioChem"},{"key":"2026090316302950600_cit28","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jmb.2011.12.032","article-title":"Sensitivity of amyloid\nformation by human islet amyloid polypeptide to mutations at residue\n20","volume":"421","author":"Cao","year":"2012","journal-title":"J. Mol. Biol."},{"key":"2026090316302950600_cit29","doi-asserted-by":"crossref","first-page":"23959","DOI":"10.1074\/jbc.M111.226688","article-title":"Hexafluoroisopropanol induces amyloid\nfibrils of islet amyloid polypeptide\nby enhancing both hydrophobic and electrostatic interactions","volume":"286","author":"Yanagi","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2026090316302950600_cit30","doi-asserted-by":"crossref","first-page":"22715","DOI":"10.1074\/jbc.M011499200","article-title":"Is Congo red an\namyloid-specific dye?","volume":"276","author":"Khurana","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2026090316302950600_cit31","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1021\/ol047480+","article-title":"Incorporation of\npseudoproline derivatives allows the\nfacile synthesis of human IAPP, a highly amyloidogenic and aggregation-prone\npolypeptide","volume":"7","author":"Abedini","year":"2005","journal-title":"Org. Lett."},{"key":"2026090316302950600_cit32","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1021\/ol101981b","article-title":"Efficient\nmicrowave-assisted synthesis of human islet amyloid polypeptide designed\nto facilitate the specific incorporation of labeled amino acids","volume":"12","author":"Marek","year":"2010","journal-title":"Org. Lett."},{"key":"2026090316302950600_cit33","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ab.2005.11.029","article-title":"Recovery and purification of highly\naggregation-prone disulfide-containing peptides: Application to islet\namyloid polypeptide","volume":"351","author":"Abedini","year":"2006","journal-title":"Anal. Biochem."},{"key":"2026090316302950600_cit34","doi-asserted-by":"crossref","first-page":"6657","DOI":"10.1021\/ja00017a044","article-title":"Disulfide bond formation\nin peptides by dimethyl-sulfoxide \u2013 Scope and applications","volume":"113","author":"Tam","year":"1991","journal-title":"J. Am. 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