{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:03Z","timestamp":1792789083299,"version":"4.5.0"},"reference-count":201,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University in Lublin","award":["450\/22"],"award-info":[{"award-number":["450\/22"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The tryptophan\u2013kynurenine pathway (Trp\u2013KYN) is the major route for tryptophan conversion in the brain and in the periphery. Kynurenines display a wide range of biological actions (which are often contrasting) such as cytotoxic\/cytoprotective, oxidant\/antioxidant or pro-\/anti-inflammatory. The net effect depends on their local concentration, cellular environment, as well as a complex positive and negative feedback loops. The imbalance between beneficial and harmful kynurenines was implicated in the pathogenesis of various neurodegenerative disorders, psychiatric illnesses and metabolic disorders, including diabetes mellitus (DM). Despite available therapies, DM may lead to serious macro- and microvascular complications including cardio- and cerebrovascular disease, peripheral vascular disease, chronic renal disease, diabetic retinopathy, autonomic neuropathy or cognitive impairment. It is well established that low-grade inflammation, which often coincides with DM, can affect the function of KP and, conversely, that kynurenines may modulate the immune response. This review provides a detailed summary of findings concerning the status of the Trp\u2013KYN pathway in DM based on available animal, human and microbiome studies. We highlight the importance of the molecular interplay between the deranged (functionally and qualitatively) conversion of Trp to kynurenines in the development of DM and insulin resistance. The Trp\u2013KYN pathway emerges as a novel target in the search for preventive and therapeutic interventions in DM.<\/jats:p>","DOI":"10.3390\/cells12030460","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T03:22:47Z","timestamp":1675221767000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Kynurenine Pathway in Diabetes Mellitus\u2014Novel Pharmacological Target?"],"prefix":"10.3390","volume":"12","author":[{"given":"Kamila","family":"Kozie\u0142","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Chair and Department of Clinical and Experimental Pharmacology, Medical University, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-528X","authenticated-orcid":false,"given":"Ewa M.","family":"Urbanska","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Pharmacology, Chair and Department of Clinical and Experimental Pharmacology, Medical University, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.tips.2020.11.006","article-title":"Tryptophan Metabolism as a Pharmacological Target","volume":"42","author":"Modoux","year":"2020","journal-title":"Trends Pharmacol. 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