{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:43:30Z","timestamp":1791287010733,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T00:00:00Z","timestamp":1612310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 1 diabetes mellitus is an autoimmune disease characterized by increased production of pro-inflammatory cytokines secreted by infiltrating macrophages and T cells that destroy pancreatic \u03b2 cells in a free radical-dependent manner that causes decrease or absence of insulin secretion and consequent hyperglycemia. Hence, suppression of pro-inflammatory cytokines and oxidative stress may ameliorate or decrease the severity of diabetes mellitus. To investigate the effect and mechanism(s) of action of RVD1, an anti-inflammatory metabolite derived from docosahexaenoic acid (DHA), on STZ-induced type 1 DM in male Wistar rats, type 1 diabetes was induced by single intraperitoneal (i.p) streptozotocin (STZ-65 mg\/kg) injection. RVD1 (60 ng\/mL, given intraperitoneally) was administered from day 1 along with STZ for five consecutive days. Plasma glucose, IL-6, TNF-\u03b1, BDNF (brain-derived neurotrophic factor that has anti-diabetic actions), LXA4 (lipoxin A4), and RVD1 levels and BDNF concentrations in the pancreas, liver, and brain tissues were measured. Apoptotic (Bcl2\/Bax), inflammatory (COX-1\/COX-2\/Nf-\u03bab\/iNOS\/PPAR-\u03b3) genes and downstream insulin signaling proteins (Gsk-3\u03b2\/Foxo1) were measured in the pancreatic tissue along with concentrations of various antioxidants and lipid peroxides. RVD1 decreased severity of STZ-induced type 1 DM by restoring altered plasma levels of TNF-\u03b1, IL-6, and BDNF (p &lt; 0.001); expression of pancreatic COX-1\/COX-2\/PPAR-\u03b3 genes and downstream insulin signaling proteins (Gsk-3\u03b2\/Foxo1) and the concentrations of antioxidants and lipid peroxides to near normal. RVD1 treatment restored expression of Bcl2\/Pdx genes, plasma LXA4 (p &lt; 0.001) and RVD1 levels and increased brain, pancreatic, intestine, and liver BDNF levels to near normal. The results of the present study suggest that RVD1 can prevent STZ-induced type 1 diabetes by its anti-apoptotic, anti-inflammatory, and antioxidant actions and by activating the Pdx gene that is needed for pancreatic \u03b2 cell proliferation.<\/jats:p>","DOI":"10.3390\/ijms22041516","type":"journal-article","created":{"date-parts":[[2021,2,3]],"date-time":"2021-02-03T20:31:51Z","timestamp":1612384311000},"page":"1516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Resolvin D1 Decreases Severity of Streptozotocin-Induced Type 1 Diabetes Mellitus by Enhancing BDNF Levels, Reducing Oxidative Stress, and Suppressing Inflammation"],"prefix":"10.3390","volume":"22","author":[{"given":"Siresha","family":"Bathina","sequence":"first","affiliation":[{"name":"BioScience Research Centre and Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India"},{"name":"Department of Biotechnology, Gandhi Institute of Science (GIS), GITAM University, Visakhapatnam 530048, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0191-9508","authenticated-orcid":false,"given":"Undurti N.","family":"Das","sequence":"additional","affiliation":[{"name":"BioScience Research Centre and Department of Medicine, Gayatri Vidya Parishad Hospital, GVP College of Engineering Campus, Visakhapatnam 530048, India"},{"name":"UND Life Sciences, 2221 NW 5th St, Battle Ground, WA 98604, USA"},{"name":"International Research Centre, Biotechnologies of the Third Millennium, ITMO University, 191002 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.it.2013.08.005","article-title":"Immune mechanisms in type 1 diabetes","volume":"34","author":"Wallberg","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.2337\/db10-1797","article-title":"How does type 1 diabetes develop? 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