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However, T2D is a risk factor for AD, and recent evidence suggests there are many mechanistic similarities between the etiologies of each disease including inflammation. Mast cells are tissue resident, sentinel immune cells that reside in the pancreas, adipose tissue, and brain, increase in T2D and AD, and have generally been shown to worsen T2D and AD. However, there are limited studies of local or temporal mast cell deletion, and different phenotypic and polarization states seemingly influence the role of mast cells in the progression of disease. As there are metabolic similarities between T2D and AD including insulin resistance and lipid influx into the brain, we discuss the impact of glucose, insulin, amylin, and different lipid species on the activation and polarization of mast cells, which generally reduce IgE\u2010mediated degranulation and promote lipid droplet formation and arachidonic acid metabolism. Altogether, this review provides a framework for understanding a shared mechanism of immunometabolic regulation of T2D and AD and provides rationale for future work in this area.<\/jats:p>","DOI":"10.1002\/jcp.70091","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T11:05:17Z","timestamp":1757934317000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mast Cell Immunometabolism in Type 2 Diabetes and Alzheimer's Disease"],"prefix":"10.1002","volume":"240","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-6779","authenticated-orcid":false,"given":"Heather L.","family":"Caslin","sequence":"first","affiliation":[{"name":"Department of Health and Human Performance University of Houston Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munira","family":"Kapadia","sequence":"additional","affiliation":[{"name":"Department of Health and Human Performance University of Houston Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tameka A.","family":"Clemons","sequence":"additional","affiliation":[{"name":"Tilman J. 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