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Serum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment

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dc.contributor.author강원준-
dc.contributor.author구철룡-
dc.contributor.author권인규-
dc.contributor.author노성훈-
dc.contributor.author박종필-
dc.contributor.author성학준-
dc.contributor.author신수진-
dc.contributor.author윤미진-
dc.contributor.author이은직-
dc.contributor.author조응혁-
dc.contributor.author형우진-
dc.contributor.author강찬우-
dc.date.accessioned2021-10-21T00:07:54Z-
dc.date.available2021-10-21T00:07:54Z-
dc.date.issued2021-10-
dc.identifier.issn0017-5749-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/185390-
dc.description.abstractObjective: The mechanisms underlying type 2 diabetes resolution after Roux-en-Y gastric bypass (RYGB) are unclear. We suspected that glucose excretion may occur in the small bowel based on observations in humans. The aim of this study was to evaluate the mechanisms underlying serum glucose excretion in the small intestine and its contribution to glucose homeostasis after bariatric surgery. Design: 2-Deoxy-2-[18F]-fluoro-D-glucose (FDG) was measured in RYGB-operated or sham-operated obese diabetic rats. Altered glucose metabolism was targeted and RNA sequencing was performed in areas of high or low FDG uptake in the ileum or common limb. Intestinal glucose metabolism and excretion were confirmed using 14C-glucose and FDG. Increased glucose metabolism was evaluated in IEC-18 cells and mouse intestinal organoids. Obese or ob/ob mice were treated with amphiregulin (AREG) to correlate intestinal glycolysis changes with changes in serum glucose homeostasis. Results: The AREG/EGFR/mTOR/AKT/GLUT1 signal transduction pathway was activated in areas of increased glycolysis and intestinal glucose excretion in RYGB-operated rats. Intraluminal GLUT1 inhibitor administration offset improved glucose homeostasis in RYGB-operated rats. AREG-induced signal transduction pathway was confirmed using IEC-18 cells and mouse organoids, resulting in a greater capacity for glucose uptake via GLUT1 overexpression and sequestration in apical and basolateral membranes. Systemic and local AREG administration increased GLUT1 expression and small intestinal membrane translocation and prevented hyperglycaemic exacerbation. Conclusion: Bariatric surgery or AREG administration induces apical and basolateral membrane GLUT1 expression in the small intestinal enterocytes, resulting in increased serum glucose excretion in the gut lumen. Our findings suggest a novel, potentially targetable glucose homeostatic mechanism in the small intestine.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherBritish Medical Assn.-
dc.relation.isPartOfGUT-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleSerum glucose excretion after Roux-en-Y gastric bypass: a potential target for diabetes treatment-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Nuclear Medicine (핵의학교실)-
dc.contributor.googleauthorIn Gyu Kwon-
dc.contributor.googleauthorChan Woo Kang-
dc.contributor.googleauthorJong-Pil Park-
dc.contributor.googleauthorJu Hun Oh-
dc.contributor.googleauthorEun Kyung Wang-
dc.contributor.googleauthorTae Young Kim-
dc.contributor.googleauthorJin Sol Sung-
dc.contributor.googleauthorNamhee Park-
dc.contributor.googleauthorYang Jong Lee-
dc.contributor.googleauthorHak-Joon Sung-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorWoo Jin Hyung-
dc.contributor.googleauthorSu-Jin Shin-
dc.contributor.googleauthorSung Hoon Noh-
dc.contributor.googleauthorMijin Yun-
dc.contributor.googleauthorWon Jun Kang-
dc.contributor.googleauthorArthur Cho-
dc.contributor.googleauthorCheol Ryong Ku-
dc.identifier.doi10.1136/gutjnl-2020-321402-
dc.contributor.localIdA00062-
dc.contributor.localIdA00201-
dc.contributor.localIdA00243-
dc.contributor.localIdA01281-
dc.contributor.localIdA01665-
dc.contributor.localIdA01958-
dc.contributor.localIdA04596-
dc.contributor.localIdA02550-
dc.contributor.localIdA03050-
dc.contributor.localIdA03887-
dc.contributor.localIdA04382-
dc.relation.journalcodeJ00953-
dc.identifier.eissn1468-3288-
dc.identifier.pmid33208408-
dc.identifier.urlhttps://gut.bmj.com/content/70/10/1847.long-
dc.subject.keyworddiabetes mellitus-
dc.subject.keywordepidermal growth factor-
dc.subject.keywordgastrectomy-
dc.subject.keywordglucose metabolism-
dc.contributor.alternativeNameKang, Won Jun-
dc.contributor.affiliatedAuthor강원준-
dc.contributor.affiliatedAuthor구철룡-
dc.contributor.affiliatedAuthor권인규-
dc.contributor.affiliatedAuthor노성훈-
dc.contributor.affiliatedAuthor박종필-
dc.contributor.affiliatedAuthor성학준-
dc.contributor.affiliatedAuthor신수진-
dc.contributor.affiliatedAuthor윤미진-
dc.contributor.affiliatedAuthor이은직-
dc.contributor.affiliatedAuthor조응혁-
dc.contributor.affiliatedAuthor형우진-
dc.citation.volume70-
dc.citation.number10-
dc.citation.startPage1847-
dc.citation.endPage1856-
dc.identifier.bibliographicCitationGUT, Vol.70(10) : 1847-1856, 2021-10-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Forensic Medicine (법의학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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