Progression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus rat

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dc.contributor.authorPiccolo, Brian D.en
dc.contributor.authorGraham, James L.en
dc.contributor.authorKang, Pingen
dc.contributor.authorRandolph, Christopher E.en
dc.contributor.authorShankar, Kartiken
dc.contributor.authorYeruva, Laxmien
dc.contributor.authorFox, Reneeen
dc.contributor.authorRobeson, Michael S.en
dc.contributor.authorMoody, Beckyen
dc.contributor.authorLeRoith, Tanyaen
dc.contributor.authorStanhope, Kimber L.en
dc.contributor.authorAdams, Sean H.en
dc.contributor.authorHavel, Peter J.en
dc.date.accessioned2022-02-24T18:37:37Zen
dc.date.available2022-02-24T18:37:37Zen
dc.date.issued2021-11-01en
dc.date.updated2022-02-24T18:37:34Zen
dc.description.abstractDeterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model. Male UCD-T2DM rats (age ~170 days) were included if <1-month (n = 6, D1M) or 3-month (n = 6, D3M) post-onset of diabetes. Younger nondiabetic UCD-T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD-T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.en
dc.description.versionPublished versionen
dc.format.extentPages e15102en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.14814/phy2.15102en
dc.identifier.eissn2051-817Xen
dc.identifier.issn2051-817Xen
dc.identifier.issue22en
dc.identifier.orcidLeRoith, Tanya [0000-0002-1196-6949]en
dc.identifier.pmid34806320en
dc.identifier.urihttp://hdl.handle.net/10919/108852en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/34806320en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectRNA-seqen
dc.subjectUCD-T2DM raten
dc.subjectcrypten
dc.subjectdiabetesen
dc.subjectmicrobiomeen
dc.subjectvillien
dc.subject0606 Physiologyen
dc.subject1103 Clinical Sciencesen
dc.subject1116 Medical Physiologyen
dc.titleProgression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus raten
dc.title.serialPhysiological Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2021-10-18en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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