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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The pathological assessment of diabetes mellitus (DM) in humans is frequently confounded by glucose-lowering therapies. Untreated spontaneously diabetic rhesus macaques (Macaca mulatta) provide a valuable model for elucidating the authentic pathology of the disease. In this study, we performed histopathological, immunohistochemical, and transcriptomic analyses on the pancreas, liver, and skeletal muscle of a spontaneous diabetic macaque alongside healthy controls. The results demonstrate that the pancreas exhibited the most severe histopathological damage, with extensive acinar destruction, apoptosis, and prominent IL-17-mediated inflammation, underpinned by activation of the p53 signaling pathway and suppression of exocrine secretion genes. In the liver, damage is driven primarily by innate immune activation and metabolic inflammation, manifesting as metabolic dysfunction-associated steatotic liver disease (MASLD)-like steatotic lesions and insulin resistance-related cytokine expression. In skeletal muscle, endoplasmic reticulum stress emerges as a key molecular event linked to muscle fiber atrophy. Cross-species comparison with human T2DM pancreatic data further identified 20 conserved differentially expressed genes (DEGs) involved in insulin\/IGF signaling and chronic inflammation. Collectively, these findings provide a multi-organ perspective on diabetes-induced pathological and transcriptional alterations and underscore the translational relevance of the macaque model for human diabetes research.<\/jats:p>","DOI":"10.3390\/ijms27177794","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Histopathological and Transcriptomic Alterations in Metabolic Organs: A Case Study from a Spontaneously Diabetic Rhesus Macaque"],"prefix":"10.3390","volume":"27","author":[{"given":"Qi","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Animal Experimental Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Yuchen","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"given":"Wen","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Qinghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Animal Experimental Center, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3242-4495","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Bio-Resources and Eco-Environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu 610065, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"#cr-split#-ref_1.1","unstructured":"GBD 2021 Diabetes Collaborators (2023). 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