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Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes

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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.

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Acknowledgements

The authors thank Dr. Fabio Manenti for technical assistance in immunofluorescence imaging.

Funding

This work was supported in part by a EFSD/JDRF/Lilly 2017 award to VS.

Author information

Authors and Affiliations

  1. Diabetes Research Institute, IRCCS San Raffaele Hospital, 20132, Milan, Italy

    Andrea Mario Bolla, Elena Butera, Silvia Pellegrini, Amelia Caretto, Valeria Sordi & Emanuele Bosi

  2. San Raffaele Vita Salute University, Via Olgettina 60, 20132, Milan, Italy

    Elena Butera, Giulia Martina Cavestro & Emanuele Bosi

  3. Pediatrics and Neonatal Disease Unit, IRCCS San Raffaele Hospital, 20132, Milan, Italy

    Riccardo Bonfanti & Graziano Barera

  4. Gastroenterology and Digestive Endoscopy Unit, IRCCS San Raffaele Hospital, 20132, Milan, Italy

    Raffaella Alessia Zuppardo & Giulia Martina Cavestro

Authors
  1. Andrea Mario Bolla
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  2. Elena Butera
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  3. Silvia Pellegrini
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  4. Amelia Caretto
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  5. Riccardo Bonfanti
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  6. Raffaella Alessia Zuppardo
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  7. Graziano Barera
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  8. Giulia Martina Cavestro
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  9. Valeria Sordi
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  10. Emanuele Bosi
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Contributions

AMB coordinated the study, contributed to samples collection and wrote the manuscript; AC, RB, RZ, GB, GMC contributed to samples collection and critically reviewed the manuscript; ElBu. SP, VS performed the experimental work, analyzed the data, contributed to data interpretation and critically reviewed the manuscript; EmBo designed and supervised the study, contributed to data interpretation and wrote the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Emanuele Bosi.

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Conflict of interest

EmBo received advisory boards, consultancy and lectures fees from AstraZeneca and Lexicon Pharmaceuticals. No other dualities relevant to this article are reported by the remaining authors.

Ethical standard statement

The study was approved by the Ethics Committee of the San Raffaele Hospital and was conducted according to the Declaration of Helsinki standards.

Informed consent

Written informed consent was obtained from all adult and from parents of children participating to the study, before biopsy collection.

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Managed by Antonio Secchi.

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Bolla, A.M., Butera, E., Pellegrini, S. et al. Expression of glucose transporters in duodenal mucosa of patients with type 1 diabetes. Acta Diabetol 57, 1367–1373 (2020). https://doi.org/10.1007/s00592-020-01558-w

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  • DOI: https://doi.org/10.1007/s00592-020-01558-w

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