{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:07:43Z","timestamp":1792508863098,"version":"4.5.0"},"reference-count":1239,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Government contract of the Institute of Immunology and Physiology","award":["122020900136-4"],"award-info":[{"award-number":["122020900136-4"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin resistance (IR) is a central driver of cardiometabolic disease and an increasingly recognized modifier of inflammatory and vascular pathology. Beyond impaired glucose homeostasis, IR emerges from chronic, metabolically induced inflammation (\u201cmeta-inflammation\u201d) and convergent cellular stress programs that propagate across tissues and organ systems, ultimately shaping endothelial dysfunction, atherogenesis, and cardiometabolic complications. Here, we synthesize multilevel links between insulin receptor signaling, intracellular stress modules (oxidative, endoplasmic reticulum, inflammatory, and fibrotic pathways), tissue-level dysfunction, and systemic inflammatory amplification. This work is a conceptual narrative review informed by targeted database searches and citation tracking, with explicit separation of mechanistic\/experimental evidence from human observational and interventional data; causal inferences are framed primarily on mechanistic and interventional findings, whereas associative statements are reserved for observational evidence. We propose an integrative framework in which stress-response pathways are context-dependent and become maladaptive when chronically activated under nutrient excess and persistent inflammatory cues, generating self-reinforcing loops between IR and inflammation that accelerate vascular injury. This framework highlights points of convergence that can guide mechanistic prioritization and translational hypothesis testing.<\/jats:p>","DOI":"10.3390\/ijms27031237","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T15:48:30Z","timestamp":1769442510000},"page":"1237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Insulin Resistance and Inflammation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-2376","authenticated-orcid":false,"given":"Evgenii","family":"Gusev","sequence":"first","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3101-9655","authenticated-orcid":false,"given":"Alexey","family":"Sarapultsev","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"},{"name":"A Russian\u2013Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3266-0954","authenticated-orcid":false,"given":"Yulia","family":"Zhuravleva","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.1152\/ajpendo.00441.2021","article-title":"Hyperinsulinemia: Beneficial or harmful or both on glucose homeostasis","volume":"323","author":"Xing","year":"2022","journal-title":"Am. 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