Published online Feb 21, 2018. doi: 10.3748/wjg.v24.i7.775
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
Processing time: 64 Days and 15.3 Hours
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.
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.
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.
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.
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.
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.
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.