Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2018; 24(7): 775-793
Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.775
Glucose transporter expression in the human colon
Flavia Merigo, Alessandro Brandolese, Sonia Facchin, Silvia Missaggia, Paolo Bernardi, Federico Boschi, Renata D’Incà, Edoardo Vincenzo Savarino, Andrea Sbarbati, Giacomo Carlo Sturniolo
Flavia Merigo, Silvia Missaggia, Paolo Bernardi, Andrea Sbarbati, Department of Neuroscience, Biomedicine and Movement, Human Anatomy and Histology Section, University of Verona, Verona I-37134, Italy
Alessandro Brandolese, Department of Medicine, Gastroenterology Section, University of Verona, Verona I-37134, Italy
Sonia Facchin, Renata D’Incà, Edoardo Vincenzo Savarino, Giacomo Carlo Sturniolo, Department of Surgery, Oncology and Gastroenterology, Gastroenterology Section, University Hospital of Padua, Padua I-35128, Italy
Federico Boschi, Department of Computer Science, University of Verona, Verona I-37134, Italy
Author contributions: Merigo F was involved in experimental design, immunohistochemistry, data analyses, and manuscript writing; Brandolese A contributed to clinical sample documentation, presentation of the results, and manuscript writing; Facchin S, D’Incà R and Savarino EV contributed to clinical sample collection and documentation; Missaggia S contributed to immunohistochemistry analysis; Bernardi P performed SEM analysis; Boschi F analyzed the data; Sbarbati A and Sturniolo GC were involved in experimental design, final critical reading of the manuscript before submission; all authors contributed to the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Padua University Hospital (study n° 2813P) Institutional Review Board.
Conflict-of-interest statement: All authors declare no conflicts of interest.
Data sharing statement: Technical appendix and data set are available from the corresponding author at flavia.merigo@univr.it. Participants gave informed consent for data sharing. The present data are anonymized and the risk of identification is low.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Flavia Merigo, BSc, Human Anatomy and Histology Section, Department of Neuroscience, Biomedicine and Movement, University of Verona, Strada Le Grazie 8, Verona I-37134, Italy. flavia.merigo@univr.it
Telephone: +39-45-8027155 Fax: +39-45-8027163
Received: December 6, 2017
Peer-review started: December 6, 2017
First decision: December 12, 2017
Revised: December 13, 2017
Accepted: December 19, 2017
Article in press: December 19, 2017
Published online: February 21, 2018
ARTICLE HIGHLIGHTS
Research background

Glucose transporter expression is present throughout the digestive system, greatest in the small intestine and least in the terminal ileum. Most studies to date on glucose transporters in the gastrointestinal tract have been performed using biochemical rather than standard immunohistochemical analysis also in humans.

Research motivation

The localization and distribution of glucose transporters in the intestinal mucosa of the human colon has not yet been clarified despite evidences that support the role of glucose transporters in broad areas of pure glucose absorption and metabolism, such as inflammation, malignancy, and gut microbiota regulation.

Research objectives

The aim of this study was to investigate by immunostaining at light and confocal microscopy the expression of the major intestinal glucose transporters (GLUT2, SGLT1, GLUT5) in human colonic mucosa in control subjects and subjects with IBD.

Research methods

Patients diagnosed with ulcerative colitis or Crohn’s disease and scheduled for diagnostic colonoscopy were enrolled. Patients who underwent colonoscopy for prevention screening of colorectal cancer or were followed-up after polypectomy or lower gastrointestinal symptoms were designated as the control group. Colorectal samples were obtained from patients undergoing lower endoscopic colonoscopy or recto-sigmoidoscopy. Biopsies of portions of the colonic tract (cecum, ascending colon, transverse, descending, sigmoid colon, rectum) were taken for diagnostic purposes according to the endoscopist’s judgment and for immunohistochemistry. Inflammatory status of the mucosa at the sampling site was evaluated endoscopically and histologically.

Samples were fixed in formaldehyde and embedded in paraffin. The expression of GLUT2, SGLT1, and GLUT5 glucose transporters was investigated using immunoperoxidase labeling. Immunoreactivity of GLUT5 was compared with that of LYVE-1, which is a marker for lymphatic vessel endothelium, using double-labeled confocal microscopy.

Research results

GLUT2, SGLT1, and GLUT5 glucose transporter immunostaining was found in short epithelial portions of the large intestine from IBD and control patients. No difference in glucose transporter expression was observed between the samples obtained from the proximal and distal tracts and between the different patient groups. GLUT5 immunostaining was also detected in vessels, which were mainly concentrated in specific areas. In double fluorescent-labeled sections with GLUT5 and LYVE-1, GLUT5-immunoreactive clusters of vessels were concentrated in areas internal to those that were LYVE-1 positive. The GLUT5 and LYVE-1 labeling patterns were never colocalized but rather showed a close topographical relationship on the endothelium lining the lumen. Based on their LYVE-1 expression, GLUT5 immunoreactive vessels were identified as lymphatic and observed both in inflamed and non-inflamed mucosal colorectal tissue biopsies from the IBD and CTRL patients. This novel finding yields further insight into the characterization of lymphatic vasculature, whose dysfunction is a long-recognized feature in humans with IBD.

Research conclusions

This study provides evidence that GLUT2, SGLT1, and GLUT5 glucose transporters are expressed in the colorectal mucosa in controls and IBD patients. Furthermore, it provides first evidence that GLUT5 expression is associated with lymphatic vessels in controls and IBD patients. Its expression indicates that GLUT5 may play a role in controlling the formation of lymphatic vessels. GLUT5 expression on endothelial lymphovascular cells may have implications for routine use in the histopathological evaluation of lymphangiogenesis, also in combination with LYVE-1, a marker of lymphatic endothelium that can be down-modulated under inflammatory conditions.

Research perspectives

A future area of focus is the precise function of GLUT5 expression in lymphatic vessels and the factors that interfere with the development or maintenance of IBD.