{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:27:58Z","timestamp":1786436878716,"version":"build-2736575974"},"reference-count":90,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Islet amyloid deposition derived from human islet amyloid polypeptide (hIAPP, amylin) is a hallmark of type 2 diabetes (T2D) and is tightly linked to progressive \u03b2-cell dysfunction and loss. It is now well established that the \u201ctoxic oligomer\u201d hypothesis, in which soluble or intracellular hIAPP assemblies contribute to \u03b2-cell proteotoxicity and to the amplification of inflammatory stress, coexists with fibril associated and inflammation-driven mechanisms of toxicity. Regular physical activity (PA) is a cornerstone of T2D management and improves insulin sensitivity, glycemic control, ectopic lipid handling, and systemic inflammation, all of which could reduce \u03b2-cell secretory burden and the cellular milieu that favors hIAPP misfolding. However, direct demonstrations that PA delays or reduces islet amyloid formation remain scarce. This gap largely reflects methodological constrains in quantifying amyloid dynamics in humans and the absence of exercise studies with amyloid-specific endpoints. Herein, we synthesize mechanistic links by which exercise could influence hIAPP aggregation propensity (\u03b2-cell workload, glucolipotoxicity, endoplasmic reticulum stress, mitochondrial function, and inflammatory signaling) and highlight proteostasis pathways, particularly autophagy\/lysosomal clearance, which are experimentally shown to defend \u03b2-cells against hIAPP oligomer toxicity. Overall, while direct evidence remains sparse, substantial mechanistic plausibility supports a link between PA and hIAPP amyloid biology. Future studies incorporating amyloid-specific outcomes are needed to determine whether exercise directly modifies amyloid formation, reduces oligomer burden, or primarily enhances \u03b2-cell resilience to proteotoxic stress.<\/jats:p>","DOI":"10.1210\/endocr\/bqag088","type":"journal-article","created":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T11:34:50Z","timestamp":1785670490000},"source":"Crossref","is-referenced-by-count":0,"title":["Physical activity and human islet amyloid polypeptide islet amyloidosis: mechanistic plausibility, missing evidence, and future directions"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1241-8004","authenticated-orcid":false,"given":"Joan-Marc","family":"Servitja","sequence":"first","affiliation":[{"name":"Pathogenesis and Prevention of Diabetes Group, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0465-2949","authenticated-orcid":false,"given":"Anna","family":"Novials","sequence":"additional","affiliation":[{"name":"Pathogenesis and Prevention of Diabetes Group, Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) , Barcelona 08036 ,","place":["Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM) , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9531-9580","authenticated-orcid":false,"given":"Joel","family":"Montane","sequence":"additional","affiliation":[{"name":"Facultat de Psicologia, Ci\u00e8ncies de l'Educaci\u00f3 i de l'Esport Blanquerna, Universitat Ramon Llull , Barcelona 08022 ,","place":["Spain"]},{"name":"Facultat de Ci\u00e8ncies de la Salut, Blanquerna, Universitat Ramon Llull , Barcelona 08025 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"3","key":"2026081103320427300_bqag088-B1","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1152\/physrev.00042.2009","article-title":"Islet amyloid polypeptide, islet amyloid, and diabetes mellitus","volume":"91","author":"Westermark","year":"2011","journal-title":"Physiol Rev"},{"issue":"9","key":"2026081103320427300_bqag088-B2","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.2337\/db07-0178","article-title":"Impairment of the ubiquitin-proteasome pathway is a downstream endoplasmic reticulum stress response induced by extracellular human islet amyloid polypeptide and contributes to pancreatic beta-cell 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