{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:30:44Z","timestamp":1786681844582,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010774","name":"Consejer\u00eda de Educaci\u00f3n e Investigaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    Amylin is a peptide hormone co-secreted with insulin by pancreatic \u03b2-cells that regulates glucose homeostasis and satiety. In humans, amylin exhibits a strong propensity to aggregate, contributing to \u03b2-cell dysfunction and the development of type 2 diabetes mellitus (T2D). Emerging evidence suggests that amylin aggregates may exert systemic effects beyond the pancreas, potentially affecting peripheral tissues and the brain. However,\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence supporting this multi-organ involvement remains limited. In this study, we investigated the impact of human amylin aggregation across metabolic tissues using a transgenic mouse model expressing human IAPP (TghIAPP), fed either a standard diet (STD) or a high-fat diet (HFD), and evaluated the therapeutic potential of resveratrol. HFD-fed TghIAPP mice developed impaired glucose tolerance, increased amyloid aggregation, and enhanced markers of apoptosis and senescence in pancreatic islets. These alterations were associated with activation of endoplasmic reticulum (ER) stress pathways. Resveratrol treatment significantly reduced pancreatic amyloid burden, attenuated ER stress signaling, and improved markers of \u03b2-cell integrity. In the liver, TghIAPP mice exhibited increased lipid accumulation, inflammatory markers, and amyloid oligomer deposition, although the effects of resveratrol were modest and did not consistently reach statistical significance. In the brain, amyloid aggregates were detected in the hippocampus; however, resveratrol-induced changes in aggregate load and behavioral performance were limited and should be interpreted cautiously. Overall, these findings support a robust role for amylin aggregation in pancreatic dysfunction and highlight resveratrol as a modulator of pancreatic proteotoxic stress. The observed alterations in liver and brain suggest potential systemic effects of amylin aggregates that warrant further investigation.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1871780","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:22:31Z","timestamp":1786681351000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Resveratrol modulates pancreatic proteotoxic stress and metabolic dysfunction in human IAPP transgenic mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Sarai","family":"Iglesias-Fortes","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Farmacia, Universidad Complutense de Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Cl\u00ednico San Carlos (IdISSC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Garc\u00eda-Aguilar","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Cl\u00ednico San Carlos (IdISSC)","place":["Madrid, Spain"]},{"name":"Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, Complutense University of Madrid","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"Instituto de Investigaciones Biom\u00e9dicas Sols-Monreale, Consejo Superior de Investigaciones Cient\u00edficas\/Universidad Aut\u00f3noma de Madrid","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Rodr\u00edguez-Cueto","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad Complutense","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)","place":["Madrid, Spain"]},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Fern\u00e1ndez-Ruiz","sequence":"additional","affiliation":[{"name":"Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Medicina, Universidad Complutense","place":["Madrid, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)","place":["Madrid, Spain"]},{"name":"Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olmo","family":"Mart\u00edn-C\u00e1mara","sequence":"additional","affiliation":[{"name":"Unidad de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Qu\u00edmica en Ciencias Farmac\u00e9uticas, Facultad de Farmacia, Universidad Complutense","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Carlos","family":"Men\u00e9ndez","sequence":"additional","affiliation":[{"name":"Unidad de Qu\u00edmica Org\u00e1nica y Farmac\u00e9utica, Departamento de Qu\u00edmica en Ciencias Farmac\u00e9uticas, Facultad de Farmacia, Universidad Complutense","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Benito","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Farmacia, Universidad Complutense de Madrid","place":["Madrid, Spain"]},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Cl\u00ednico San Carlos (IdISSC)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Guill\u00e9n","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda 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