{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:25:09Z","timestamp":1777508709403,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T00:00:00Z","timestamp":1602547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Veteran\u2019s Administration Merit","award":["BX003443-01"],"award-info":[{"award-number":["BX003443-01"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK-67420"],"award-info":[{"award-number":["DK-67420"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK-108054"],"award-info":[{"award-number":["DK-108054"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM121299-01A1"],"award-info":[{"award-number":["P20GM121299-01A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1\/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and Na+\/K+-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na+\/K+-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.<\/jats:p>","DOI":"10.3390\/nu12103116","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"3116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inducible Nitric Oxide Regulates Na-Glucose Co-Transport in a Spontaneous SAMP1\/YitFc Mouse Model of Chronic Ileitis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-7534","authenticated-orcid":false,"given":"Balasubramanian","family":"Palaniappan","sequence":"first","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanmuga","family":"Sundaram","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subha","family":"Arthur","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheuli","family":"Afroz","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-6740","authenticated-orcid":false,"given":"Uma","family":"Sundaram","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1365-2796.2006.01746.x","article-title":"Active sugar transport in health and disease","volume":"261","author":"Wright","year":"2007","journal-title":"J. Intern. Med."},{"key":"ref_2","unstructured":"Leonard Johnson, K.B., Ghishan, F., Merchant, J., Said, H., and Wood, J. (2006). Sugar Absorption. Physiology of Gastrointestinal Tract, Elsevier\/Academic Press. [4th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.15585\/mmwr.mm6542a3","article-title":"Prevalence of Inflammatory Bowel Disease among Adults Aged >\/=18 Years\u2014United States, 2015","volume":"65","author":"Dahlhamer","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.cell.2008.07.021","article-title":"XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease","volume":"134","author":"Kaser","year":"2008","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3181\/00379727-214-44087","article-title":"Inflammatory mediators in gastrointestinal defense and injury","volume":"214","author":"Wallace","year":"1997","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2174\/1568010054526359","article-title":"Nitric oxide production and signaling in inflammation","volume":"4","author":"Korhonen","year":"2005","journal-title":"Curr. Drug Targets-Inflamm. Allergy"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.bbamem.2011.11.005","article-title":"Na-glutamine co-transporters B 0 AT1 in villus and SN2 in crypts are differentially altered in chronically inflamed rabbit intestine","volume":"1818","author":"Saha","year":"2012","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"G467","DOI":"10.1152\/ajpgi.00503.2005","article-title":"Neutral Na-amino acid cotransport is differentially regulated by glucocorticoids in the normal and chronically inflamed rabbit small intestine","volume":"292","author":"Sundaram","year":"2007","journal-title":"Am. J. Physiol. Gastrointest."},{"key":"ref_10","first-page":"G675","article-title":"Glucocorticoids differentially regulate Na-bile acid cotransport in normal and chronically inflamed rabbit ileal villus cells","volume":"298","author":"Coon","year":"2010","journal-title":"Am. J. Physiol."},{"key":"ref_11","first-page":"G211","article-title":"Corticosteroids reverse the inhibition of Na-glucose cotransport in the chronically inflamed rabbit ileum","volume":"276","author":"Sundaram","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Brosnan, C., Lee, S., and Liu, J. (1997). Regulation of Inducible Nitric Oxide Synthase Expression in Human Glia: Implications for Inflammatory Central Nervous System Diseases, Portland Press Limited.","DOI":"10.1042\/bst0250679"},{"key":"ref_13","first-page":"147","article-title":"Inducible nitric oxide synthase in human diseases","volume":"113","author":"Fehsel","year":"1998","journal-title":"Clin. Exp. Immunol."},{"key":"ref_14","first-page":"150","article-title":"Nitric oxide and intestinal inflammation","volume":"109","author":"Kubes","year":"2000","journal-title":"Am. J. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.lfs.2003.10.042","article-title":"iNOS-mediated nitric oxide production and its regulation","volume":"75","author":"Aktan","year":"2004","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1053\/gast.1997.v112.pm9041266","article-title":"Inducible nitric oxide synthase plays a critical role in resolving intestinal inflammation","volume":"112","author":"McCafferty","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1159\/000481618","article-title":"Chronic Kidney Disease Elicits an Intestinal Inflammation Resulting in Intestinal Dysmotility Associated with the Activation of Inducible Nitric Oxide Synthesis in Rat","volume":"97","author":"Yu","year":"2018","journal-title":"Digestion"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"774","DOI":"10.3109\/0886022X.2014.884396","article-title":"Inhibition of inducible nitric oxide synthase prevents shock wave therapy induced renal injury","volume":"36","author":"Alp","year":"2014","journal-title":"Ren. Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1080\/01635580903285072","article-title":"Resveratrol and piceatannol inhibit iNOS expression and NF-\u03ba B activation in dextran sulfate sodium-induced mouse colitis","volume":"61","author":"Youn","year":"2009","journal-title":"Nutr. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.intimp.2018.01.004","article-title":"Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats with ulcerative colitis via down-regulation of iNOS and elevation of cAMP","volume":"56","author":"Khedr","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1053\/gast.2003.50148","article-title":"Emergence of perianal fistulizing disease in the SAMP1\/YitFc mouse, a spontaneous model of chronic ileitis","volume":"124","author":"Bamias","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1002\/ibd.21638","article-title":"SAMP1\/YitFc mouse strain: A spontaneous model of Crohn\u2019s disease-like ileitis","volume":"17","author":"Pizarro","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1053\/gast.2001.29568","article-title":"Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1\/Yit adoptive transfer model of Crohn\u2019s disease in mice","volume":"121","author":"Burns","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_24","first-page":"G913","article-title":"Mechanism of inhibition of Na+-glucose cotransport in the chronically inflamed rabbit ileum","volume":"273","author":"Sundaram","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_25","first-page":"G483","article-title":"Unique mechanism of inhibition of Na+-amino acid cotransport during chronic ileal inflammation","volume":"275","author":"Sundaram","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"C1533","DOI":"10.1152\/ajpcell.2001.281.5.C1533","article-title":"NHE3-dependent cytoplasmic alkalinization is triggered by Na(+)-glucose cotransport in intestinal epithelia. American journal of physiology","volume":"281","author":"Turner","year":"2001","journal-title":"Cell Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0003-2697(83)90356-1","article-title":"Assay of Na,K-ATPase in plasma membrane preparations: Increasing the permeability of membrane vesicles using sodium dodecyl sulfate buffered with bovine serum albumin","volume":"128","author":"Forbush","year":"1983","journal-title":"Anal. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.bbamem.2012.08.003","article-title":"Prostaglandins, not the leukotrienes, regulate Cl\u2212\/HCO3\u2212 exchange (DRA, SLC26A3) in villus cells in the chronically inflamed rabbit ileum","volume":"1828","author":"Manoharan","year":"2013","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"450","DOI":"10.2350\/14-07-1529-OA.1","article-title":"Histopathology of duodenal mucosal lesions in pediatric patients with inflammatory bowel disease: Statistical analysis to identify distinctive features","volume":"17","author":"Hardee","year":"2014","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1093\/ecco-jcc\/jjy212","article-title":"Distinct histopathological features at diagnosis of very early onset inflammatory bowel disease","volume":"13","author":"Conrad","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1136\/gut.13.11.880","article-title":"The absorption and secretion of water and electrolytes across the healthy and the diseased human colonic mucosa measured in vitro","volume":"13","author":"Archampong","year":"1972","journal-title":"Gut"},{"key":"ref_32","first-page":"915","article-title":"Jejunal absorption of water and electrolytes in inflammatory bowel disease","volume":"76","author":"Binder","year":"1970","journal-title":"J. Lab. Clin. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Powell, D. (2010). Immunophysiology of intestinal electrolyte transport. Compr. Physiol., 591\u2013641.","DOI":"10.1002\/cphy.cp060425"},{"key":"ref_34","unstructured":"Lebenthal, E., and Duffey, M. (1990). Immunological regulation of electrolyte transport. Textbook of Secretory Diarrhea, Raven Press."},{"key":"ref_35","unstructured":"Field, M. (1991). Mechanisms of diarrhea in intestinal inflammation and hypersensitivity: Immune system modulation of intestinal transport. Diarrheal Diseases, Elsevier Science Publishing Co., Inc."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"G732","DOI":"10.1152\/ajpgi.1997.272.4.G732","article-title":"Effect of chronic inflammation on electrolyte transport in rabbit ileal villus and crypt cells","volume":"272","author":"Sundaram","year":"1997","journal-title":"Am. J. Physiol. Gastrointest."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.niox.2014.12.006","article-title":"Inducible nitric oxide regulates intestinal glutamine assimilation during chronic intestinal inflammation","volume":"44","author":"Arthur","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/cphy.c190016","article-title":"Mechanisms of Regulation of Transporters of Amino Acid Absorption in Inflammatory Bowel Diseases","volume":"10","author":"Singh","year":"2020","journal-title":"Compr. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3389\/fphys.2013.00347","article-title":"Post-translational regulation of endothelial nitric oxide synthase in vascular endothelium","volume":"4","author":"Qian","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.bbamem.2014.01.002","article-title":"Regulation of sodium glucose co-transporter SGLT1 through altered glycosylation in the intestinal epithelial cells","volume":"1838","author":"Arthur","year":"2014","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Manoharan, P., Sundaram, S., Singh, S., and Sundaram, U. (2018). Inducible nitric oxide regulates brush border membrane Na-glucose co-transport, but not Na: H exchange via p38 MAP kinase in intestinal epithelial cells. Cells, 7.","DOI":"10.3390\/cells7080111"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:20:04Z","timestamp":1760178004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,13]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["nu12103116"],"URL":"https:\/\/doi.org\/10.3390\/nu12103116","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,13]]}}}