{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T05:55:41Z","timestamp":1790488541015,"version":"4.1.0"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"33","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,8,18]]},"abstract":"<jats:p>\n                    \u03b2-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.662,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001) and HbA1c (\n                    <jats:italic>r<\/jats:italic>\n                    = 0.726,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative \u03b2-cell volume, and increased relative \u03b1-cell volume and hyperglucagonemia. These results strongly support the concept that IA and \u03b2-cell apoptosis in concert with \u03b1-cell proliferation and hypertrophy are key determinants of islets of Langerhans \u201cdysfunctional remodeling\u201d and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.519,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0906471106","type":"journal-article","created":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T21:49:58Z","timestamp":1248990598000},"page":"13992-13997","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":149,"title":["Pancreatic islet amyloidosis, \u03b2-cell apoptosis, and \u03b1-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons"],"prefix":"10.1073","volume":"106","author":[{"given":"Rodolfo","family":"Guardado-Mendoza","sequence":"first","affiliation":[{"name":"Department of Medicine Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto M.","family":"Davalli","sequence":"additional","affiliation":[{"name":"San Raffaele Scientific Institute, 20132 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto O.","family":"Chavez","sequence":"additional","affiliation":[{"name":"Department of Medicine Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene B.","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Southwest Foundation for Biomedical Research and Southwest National Primate Research Center, San Antonio, TX 78227;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J.","family":"Dick","sequence":"additional","affiliation":[{"name":"Southwest Foundation for Biomedical Research and Southwest National Primate Research Center, San Antonio, TX 78227;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Majluf-Cruz","sequence":"additional","affiliation":[{"name":"Unidad de Investigacion Medica en Trombosis y Aterogenesis, HGR #1 Gabriel Mancera, D.F. Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos E.","family":"Tene-Perez","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colima, C.P. 28040 Colima, Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of California, Los Angeles\u2013Department of Energy Institute of Genomics and Proteomics, Los Angeles, CA 90095-1570;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Health Science Center and Department of Veterans Affairs Audie Murphy Division, Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX 78229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Perego","sequence":"additional","affiliation":[{"name":"Department of Molecular Sciences Applied to Biosystems, University of Milan, 20134 Milan, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony G.","family":"Comuzzie","sequence":"additional","affiliation":[{"name":"Unidad de Investigacion Medica en Trombosis y Aterogenesis, HGR #1 Gabriel Mancera, D.F. Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elizabeth","family":"Tejero","sequence":"additional","affiliation":[{"name":"Unidad de Investigacion Medica en Trombosis y Aterogenesis, HGR #1 Gabriel Mancera, D.F. Mexico;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Finzi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ospedale di Circolo, Department of Human Morphology, University of Insubria, and Centro Insubre di Biotecnologie per la Salute Umana, 21100 Varese, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Placidi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ospedale di Circolo, Department of Human Morphology, University of Insubria, and Centro Insubre di Biotecnologie per la Salute Umana, 21100 Varese, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"La Rosa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ospedale di Circolo, Department of Human Morphology, University of Insubria, and Centro Insubre di Biotecnologie per la Salute Umana, 21100 Varese, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Capella","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ospedale di Circolo, Department of Human Morphology, University of Insubria, and Centro Insubre di Biotecnologie per la Salute Umana, 21100 Varese, Italy;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn","family":"Halff","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Texas Health Science Center, San Antonio, TX 78229; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Department of Medicine Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78229;"},{"name":"Fondazione G. Monasterio and Institute of Clinical Physiology, National Research Council, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A.","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"Department of Medicine Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78229;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Folli","sequence":"additional","affiliation":[{"name":"Department of Medicine Diabetes Division, University of Texas Health Science Center, San Antonio, TX 78229;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,8,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1263-9"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1837"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.68.040104.124723"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S16"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.6.1290"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00403322"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01660981"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.2007.S172"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.11.2759"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200008103430607"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.23.8628"},{"key":"e_1_3_3_13_2","first-page":"414","article-title":"Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone","volume":"127","author":"Westermark P","year":"1987","unstructured":"P Westermark, C Wernstedt, TD O'Brien, DW Hayden, KH Johnson, Islet amyloid in type 2 human diabetes mellitus and adult diabetic cats contains a novel putative polypeptide hormone. 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