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Beyond their classical roles as immune sentinels, accumulating evidence indicates that IRMs dynamically integrate \u03b2\u2010cell activity, environmental cues, and metabolic stress, thereby coordinating islet homeostasis, adaptive remodelling, and disease progression. However, their context\u2010dependent functions and therapeutic potential remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Acquisition<\/jats:title>\n                    <jats:p>This review summarizes current evidence regarding IRM origins, phenotype, metabolic plasticity, and bidirectional crosstalk with \u03b2 cells in health, type 1 diabetes, and type 2 diabetes. We further review emerging therapeutic concepts targeting macrophage metabolism, intercellular communication, and organelle function, while discussing current challenges in translating findings from murine IRMs to human disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Synthesis<\/jats:title>\n                    <jats:p>Under physiological conditions, IRMs maintain islet integrity through surveillance, efferocytosis, trophic signalling, redox control, and maintenance of intercellular communication within the islet niche. In diabetes, chronic glucolipotoxicity, autoimmunity, oxidative stress, and amyloid\u2010associated injury can redirect these homeostatic programs toward maladaptive inflammatory states that impair insulin secretion and accelerate \u03b2\u2010cell loss. Collectively, these findings support a unified framework in which IRMs act as immunometabolic hubs integrating local and systemic signals to determine \u03b2\u2010cell fate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>IRMs represent central immunometabolic hubs that orchestrate \u03b2\u2010cell fate during health and diabetes. Emerging therapeutic strategies targeting macrophage metabolism, intercellular communication, and organelle function may help prioritize future mechanistic studies and guide safer macrophage\u2010centered interventions for diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71154","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:53:13Z","timestamp":1785415993000},"page":"9794-9808","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Islet\u2010Resident Macrophages as Dynamic Immunometabolic Integrators of \u03b2\u2010Cell Fate in Health and Diabetes"],"prefix":"10.1111","volume":"28","author":[{"given":"Xiaoyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University  Jinan China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chronic Metabolic Diseases Institute of Endocrine and Metabolic Diseases of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-3559","authenticated-orcid":false,"given":"Anwen","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University  Jinan China"},{"name":"Department of Thyroid Surgery, General Surgery Qilu Hospital of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University  Jinan China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chronic Metabolic Diseases Institute of Endocrine and Metabolic Diseases of Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Qilu Hospital of Shandong University  Jinan China"},{"name":"Shandong Provincial Key Laboratory of Spatiotemporal Regulation and Precision Intervention in Endocrine and Metabolic Diseases; Shandong Provincial Engineering Research Center for Advanced Technologies in Prevention and Treatment of Chronic Metabolic Diseases Institute of Endocrine and Metabolic Diseases of Shandong University  Jinan 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