{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:06:38Z","timestamp":1767924398135,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T00:00:00Z","timestamp":1631491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian National Research, Development and Innovation Fund projects","award":["GINOP-2.3.3-15-2016-00006"],"award-info":[{"award-number":["GINOP-2.3.3-15-2016-00006"]}]},{"name":"Hungarian NKFIH fund project","award":["FK131789 (to N.B.)"],"award-info":[{"award-number":["FK131789 (to N.B.)"]}]},{"name":"J\u00e1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences","award":["to N.B."],"award-info":[{"award-number":["to N.B."]}]},{"name":"New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund","award":["No. \u00daNKP-20-5 (to N.B.)"],"award-info":[{"award-number":["No. \u00daNKP-20-5 (to N.B.)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tumour necrosis factor alpha (TNF\u03b1) is essential in neuroinflammatory modulation. Therefore, the goal of this study is to reveal the effects of chronic hyperglycaemia and insulin treatment on TNF\u03b1 expression in different gut segments and intestinal wall layers. TNF\u03b1 expression was mapped by fluorescent immunohistochemistry and quantitative immunogold electron microscopy in myenteric ganglia of duodenum, ileum and colon. Tissue TNF\u03b1 levels were measured by enzyme-linked immunosorbent assays in muscle\/myenteric plexus-containing (MUSCLE-MP) and mucosa\/submucosa\/submucous plexus-containing (MUC-SUBMUC-SP) homogenates. Increasing density of TNF\u03b1-labelling gold particles is observed in myenteric ganglia from proximal to distal segments and TNF\u03b1 tissue levels are much more elevated in MUSCLE-MP homogenates than in MUC-SUBMUC-SP samples in healthy controls. In the diabetics, the number of TNF\u03b1 gold labels is significantly increased in the duodenum, decreased in the colon and remained unchanged in the ileal ganglia, while insulin does not prevent these diabetes-related TNF\u03b1 changes. TNF\u03b1 tissue concentration is also increased in MUSCLE-MP homogenates of diabetic duodenum, while decreased in MUC-SUBMUC-SP samples of diabetic ileum and colon. These findings support that type 1 diabetes has region-specific and intestinal layer-dependent effects on TNF\u03b1 expression, contributing to the regional damage of myenteric neurons and their intestinal milieu.<\/jats:p>","DOI":"10.3390\/cells10092410","type":"journal-article","created":{"date-parts":[[2021,9,13]],"date-time":"2021-09-13T21:37:12Z","timestamp":1631569032000},"page":"2410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intestinal Region-Specific and Layer-Dependent Induction of TNF\u03b1 in Rats with Streptozotocin-Induced Diabetes and after Insulin Replacement"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-1387","authenticated-orcid":false,"given":"Nikolett","family":"B\u00f3di","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3674-5306","authenticated-orcid":false,"given":"Lalitha","family":"Chandrakumar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-9859","authenticated-orcid":false,"given":"Afnan","family":"al Doghmi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6343-4485","authenticated-orcid":false,"given":"Di\u00e1na","family":"Mezei","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zita","family":"Szalai","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5309-8633","authenticated-orcid":false,"given":"Bence P\u00e1l","family":"Barta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-6915","authenticated-orcid":false,"given":"J\u00e1nos","family":"Bal\u00e1zs","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3533-9461","authenticated-orcid":false,"given":"M\u00e1ria","family":"Bagy\u00e1nszki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Neuroscience, Faculty of Science and Informatics, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/j.1365-2982.2008.01255.x","article-title":"Development of the enteric nervous system: Bringing together cells, signals and genes","volume":"21","author":"Burns","year":"2009","journal-title":"Neurogastroenterol. 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