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Front Cell Dev Biol. 2021 May 28;9:688885. doi: 10.3389/fcell.2021.688885. eCollection 2021.

Expression and Function of Organic Cation Transporter 2 in Pancreas.

Frontiers in cell and developmental biology

Sandra Schorn, Ann-Kristin Dicke, Ute Neugebauer, Rita Schröter, Maren Friedrich, Stefan Reuter, Giuliano Ciarimboli

Affiliations

  1. Experimental Nephrology, Medicine Clinic D, University Hospital Münster, Münster, Germany.

PMID: 34124075 PMCID: PMC8195675 DOI: 10.3389/fcell.2021.688885

Abstract

Organic cation transporters (OCT) play an important role in mediating cellular uptake of several pharmaceuticals, such as the antidiabetic drug metformin and the platinum-derived chemotherapeutics. Since these drugs can also affect the pancreas, here it was investigated whether these transporters are expressed in this organ. An interaction between OCT2 and the glucose transporter 2 (GLUT2), which is expressed with important functional consequences in the kidneys and in the pancreas, has already been demonstrated elsewhere. Therefore, here it was further investigated whether the two proteins have a functional relationship. It was demonstrated that OCT2 is expressed in pancreas, probably in β cells of Langerhans islets, together with GLUT2. However, a co-localization was only evident in a cell-line model of rat pancreatic β cells under incubation with high glucose concentration. High glucose stimulated OCT2 expression and activity. On the other side, studies conducted in human embryonic kidney cells stably expressing OCT2, showed that overexpression of GLUT2 decreased OCT2 activity. Unfortunately, pull-down experiments aimed to confirm a physical OCT2/GLUT2 interaction were not successful. Renal glucose excretion was reduced in mice with genetic deletion of OCT2. Nonetheless, in these mice no regulation of known kidney glucose transporters was measured. Therefore, it may be speculated that OCT2 may influence cellular trafficking of GLUT2, without changing its amount. OCT2 may play a role in drug uptake of the pancreas, and its activity may be regulated by glucose and GLUT2. Vice versa, GLUT2 activity may be regulated through an interaction with OCT2.

Copyright © 2021 Schorn, Dicke, Neugebauer, Schröter, Friedrich, Reuter and Ciarimboli.

Keywords: glucose; glucose transporter; metformin; organic cation transporters; pancreas

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. FASEB J. 2012 Mar;26(3):976-86 - PubMed
  2. Diabetologia. 2015 Feb;58(2):221-32 - PubMed
  3. Pharmacol Rev. 2020 Jan;72(1):253-319 - PubMed
  4. J Am Soc Nephrol. 2005 Jun;16(6):1562-70 - PubMed
  5. Heliyon. 2019 Aug 08;5(8):e02247 - PubMed
  6. SLAS Discov. 2019 Oct;24(9):904-914 - PubMed
  7. Br J Pharmacol. 2011 Jun;163(3):546-55 - PubMed
  8. Int J Mol Sci. 2020 Sep 10;21(18): - PubMed
  9. Am J Physiol Cell Physiol. 2006 Jun;290(6):C1521-31 - PubMed
  10. Nat Genet. 2016 Sep;48(9):1055-1059 - PubMed
  11. Pharm Res. 2007 Jul;24(7):1227-51 - PubMed
  12. Mol Endocrinol. 1998 Feb;12(2):207-19 - PubMed
  13. J Physiol. 2003 Nov 15;553(Pt 1):137-45 - PubMed
  14. J Cell Physiol. 2004 Dec;201(3):420-8 - PubMed
  15. Mol Cell Biol. 2003 Nov;23(21):7902-8 - PubMed
  16. Neth J Med. 2007 Jan;65(1):36-7 - PubMed
  17. Ochsner J. 2015 Spring;15(1):45-51 - PubMed
  18. J Pharmacol Exp Ther. 1999 Mar;288(3):1192-8 - PubMed
  19. Nat Rev Endocrinol. 2014 Mar;10(3):143-56 - PubMed
  20. Diabetes. 2000 Mar;49(3):424-30 - PubMed
  21. Cell Mol Life Sci. 2009 May;66(10):1729-40 - PubMed
  22. Proc Natl Acad Sci U S A. 2013 Jul 2;110(27):11199-204 - PubMed
  23. Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):1984-1990 - PubMed
  24. J Med Chem. 2013 Feb 14;56(3):781-795 - PubMed
  25. Xenobiotica. 2008 Sep;38(9):1252-62 - PubMed
  26. Arch Toxicol. 2019 Oct;93(10):2835-2848 - PubMed
  27. Cell Physiol Biochem. 2018;47(4):1711-1720 - PubMed
  28. Biomolecules. 2019 Oct 07;9(10): - PubMed
  29. Am J Physiol Endocrinol Metab. 2009 May;296(5):E985-92 - PubMed

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