Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes
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ORIGINAL ARTICLE
Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes Andrea Mario Bolla1 · Elena Butera1,2 · Silvia Pellegrini1 · Amelia Caretto1 · Riccardo Bonfanti3 · Raffaella Alessia Zuppardo4 · Graziano Barera3 · Giulia Martina Cavestro2,4 · Valeria Sordi1 · Emanuele Bosi1,2 Received: 23 May 2020 / Accepted: 10 June 2020 © Springer-Verlag Italia S.r.l., part of Springer Nature 2020
Abstract Aims A higher SGLT1 and GLUT2 gene expression was shown in the intestine of subjects with type 2 diabetes, while no data have been reported in type 1 diabetes (T1D). The purpose of our study was to evaluate the expression of glucose transporters in duodenal mucosa of subjects with T1D, compared to healthy controls (CTRL) and to patients with celiac disease (CD), as gut inflammatory disease control group. Materials and methods Gene expression of GLUT1, GLUT2, SGLT1 and SGLT2 was quantified on duodenal mucosa biopsies of subjects with T1D (n = 19), CD (n = 16), T1D and CD (n = 6) and CTRL (n = 12), recruited at San Raffaele Hospital (Milan, Italy), between 2009 and 2018. SGLT2 expression was further evaluated by immunohistochemical and immunofluorescence staining. Results The expression of all four glucose transporters was detected in duodenal mucosa of all groups. A reduced GLUT2, SGLT1 and SGLT2 expression was observed in CD in comparison with T1D and CTRL, as expected; GLUT1 was significantly more expressed in T1D compared to CTRL. SGLT2 expression was quantified at much lower levels than other transporters, with no differences between groups. SGLT2 expression was confirmed by immunohistochemistry in a restricted number of enterocytes lining in the mucosa of intestinal villi, also shown on immunofluorescence. Conclusions Our results show that glucose transporters expression in duodenal mucosa of subjects with T1D, except an increased GLUT1, is not different from that observed in healthy controls. The expression of SGLT2 in human duodenal mucosa, although at low intensity, represents a novel finding. Keywords Glucose transporters · SGLT2 · SGLT1 · Gut mucosa · Type 1 diabetes
Introduction
Managed by Antonio Secchi. * Emanuele Bosi [email protected] 1
Diabetes Research Institute, IRCCS San Raffaele Hospital, 20132 Milan, Italy
2
San Raffaele Vita Salute University, Via Olgettina 60, 20132 Milan, Italy
3
Pediatrics and Neonatal Disease Unit, IRCCS San Raffaele Hospital, 20132 Milan, Italy
4
Gastroenterology and Digestive Endoscopy Unit, IRCCS San Raffaele Hospital, 20132 Milan, Italy
Physiologically, glucose crosses cell membranes via two different types of membrane-associated carrier proteins: the active sodium–glucose co-transporters, denominated Sglt, and the passive glucose transport facilitators, denominated Glut. Sglt mediates sodium and glucose symport across apical cell membranes, while Glut facilitates glucose to leave the cell and re-entry the blood stream across basolateral membrane [1]. Amongst the main isoforms of Sglts, Sglt1 is responsible for mos
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