{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:21:56Z","timestamp":1765808516009,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014FAPESP","doi-asserted-by":"publisher","award":["201220262-7"],"award-info":[{"award-number":["201220262-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Resveratrol (RSV) improves metabolic functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV\u2019s impact on molecular pathways in an experimental model of diabetes in cardiac and skeletal muscles and adipose tissue. Wistar rats were assigned to control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide, and RSV was administered for six weeks. In diabetic rats, RSV treatment significantly reduced collagen accumulation in cardiac and skeletal muscle tissues compared to untreated diabetic controls, although it did not restore muscle mass. Adipose tissue in diabetic rats exhibited a significant reduction of 3.4 times in collagen levels following RSV treatment. However, this reduction was not associated with any measurable improvement in tissue function. In cardiac tissue, RSV downregulated phosphorylated protein kinase B (AKT)\/AKT and phosphorylated ribosomal protein S6 (rpS6)\/rpS6 while mammalian target of rapamycin (mTOR) activity remained unchanged. In skeletal muscle, RSV suppressed rpS6 phosphorylation without affecting (mTOR) signaling. RSV enhanced mTOR and Beclin-1 expression in adipose tissue, though metabolic dysfunction persisted. RSV reduced receptors for advanced glycation end-product expression in all tissues, indicating the modulation of hyperglycemia-driven pathways. RSV improved fibrosis and signaling pathways but failed to reverse abnormal tissue growth patterns, including cardiac hypertrophy, skeletal muscle atrophy, and adipose tissue atrophy.<\/jats:p>","DOI":"10.3390\/ijms26041672","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T03:41:47Z","timestamp":1739763707000},"page":"1672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resveratrol Attenuates Fibrosis and Alters Signaling Pathways in Diabetic Cardiac and Skeletal Muscles and Adipose Tissue Without Reversing Structural Damage"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-1184","authenticated-orcid":false,"given":"C\u00e9lia Maria C\u00e1ssaro","family":"Strunz","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lises Cl\u00ednicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Roggerio","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lises Cl\u00ednicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9917-9570","authenticated-orcid":false,"given":"Paula L\u00e1zara","family":"Cruz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hipertens\u00e3o Experimental, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5673-165X","authenticated-orcid":false,"given":"Luiz Alberto","family":"Benvenuti","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Anatomia Patol\u00f3gica, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Cl\u00e1udia","family":"Irigoyen","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de An\u00e1lises Cl\u00ednicas, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-1090","authenticated-orcid":false,"given":"Antonio de Padua","family":"Mansur","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Preven\u00e7\u00e3o, Cardiopatia na Mulher e Reabilita\u00e7\u00e3o Cardiovascular, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.ecl.2021.05.005","article-title":"Prevention of Microvascular Complications of Diabetes","volume":"50","author":"Crasto","year":"2021","journal-title":"Endocrinol. 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