{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:18:00Z","timestamp":1790957880506,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-159711"],"award-info":[{"award-number":["PJT-159711"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["RGPIN-2017-06962"],"award-info":[{"award-number":["RGPIN-2017-06962"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["16GRU3711"],"award-info":[{"award-number":["16GRU3711"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"the Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["PJT-159711"],"award-info":[{"award-number":["PJT-159711"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"the Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-06962"],"award-info":[{"award-number":["RGPIN-2017-06962"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"the Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["16GRU3711"],"award-info":[{"award-number":["16GRU3711"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Complications Consortium","award":["PJT-159711"],"award-info":[{"award-number":["PJT-159711"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Complications Consortium","award":["RGPIN-2017-06962"],"award-info":[{"award-number":["RGPIN-2017-06962"]}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases Diabetic Complications Consortium","award":["16GRU3711"],"award-info":[{"award-number":["16GRU3711"]}]},{"name":"University of Toronto Banting &amp; Best Diabetes Centre","award":["PJT-159711"],"award-info":[{"award-number":["PJT-159711"]}]},{"name":"University of Toronto Banting &amp; Best Diabetes Centre","award":["RGPIN-2017-06962"],"award-info":[{"award-number":["RGPIN-2017-06962"]}]},{"name":"University of Toronto Banting &amp; Best Diabetes Centre","award":["16GRU3711"],"award-info":[{"award-number":["16GRU3711"]}]},{"name":"University of Toronto Centre for Collaborative Drug Research","award":["PJT-159711"],"award-info":[{"award-number":["PJT-159711"]}]},{"name":"University of Toronto Centre for Collaborative Drug Research","award":["RGPIN-2017-06962"],"award-info":[{"award-number":["RGPIN-2017-06962"]}]},{"name":"University of Toronto Centre for Collaborative Drug Research","award":["16GRU3711"],"award-info":[{"award-number":["16GRU3711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) can result in microvascular complications such as neuropathy, retinopathy, nephropathy, and cerebral small vessel disease, and contribute to macrovascular complications, such as heart failure, peripheral arterial disease, and large vessel stroke. T2DM also increases the risks of depression and dementia for reasons that remain largely unclear. Perturbations in the cytochrome P450-soluble epoxide hydrolase (CYP-sEH) pathway have been implicated in each of these diabetes complications. Here we review evidence from the clinical and animal literature suggesting the involvement of the CYP-sEH pathway in T2DM complications across organ systems, and highlight possible mechanisms (e.g., inflammation, fibrosis, mitochondrial function, endoplasmic reticulum stress, the unfolded protein response and autophagy) that may be relevant to the therapeutic potential of the pathway. These mechanisms may be broadly relevant to understanding, preventing and treating microvascular complications affecting the brain and other organ systems in T2DM.<\/jats:p>","DOI":"10.3390\/ijms23116232","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T11:05:02Z","timestamp":1654167902000},"page":"6232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Soluble Epoxide Hydrolase and Diabetes Complications"],"prefix":"10.3390","volume":"23","author":[{"given":"Natasha Z.","family":"Anita","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King\u2019s College Circle Room 4207, Toronto, ON M5S 1A8, Canada"},{"name":"Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada"},{"name":"Rumsey Centre Cardiac Rehabilitation, University Health Network Toronto Rehabilitation Institute, 347 Rumsey Rd, East York, ON M4G 2V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0030-8908","authenticated-orcid":false,"given":"Walter","family":"Swardfager","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Toronto, Medical Sciences Building, 1 King\u2019s College Circle Room 4207, Toronto, ON M5S 1A8, Canada"},{"name":"Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada"},{"name":"Rumsey Centre Cardiac Rehabilitation, University Health Network Toronto Rehabilitation Institute, 347 Rumsey Rd, East York, ON M4G 2V6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2019). 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