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Expression and Function of Organic Cation Transporter 2 in Pancreas

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 ar...

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Autores principales: Schorn, Sandra, Dicke, Ann-Kristin, Neugebauer, Ute, Schröter, Rita, Friedrich, Maren, Reuter, Stefan, Ciarimboli, Giuliano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195675/
https://www.ncbi.nlm.nih.gov/pubmed/34124075
http://dx.doi.org/10.3389/fcell.2021.688885
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author Schorn, Sandra
Dicke, Ann-Kristin
Neugebauer, Ute
Schröter, Rita
Friedrich, Maren
Reuter, Stefan
Ciarimboli, Giuliano
author_facet Schorn, Sandra
Dicke, Ann-Kristin
Neugebauer, Ute
Schröter, Rita
Friedrich, Maren
Reuter, Stefan
Ciarimboli, Giuliano
author_sort Schorn, Sandra
collection PubMed
description 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.
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spelling pubmed-81956752021-06-12 Expression and Function of Organic Cation Transporter 2 in Pancreas Schorn, Sandra Dicke, Ann-Kristin Neugebauer, Ute Schröter, Rita Friedrich, Maren Reuter, Stefan Ciarimboli, Giuliano Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-05-28 /pmc/articles/PMC8195675/ /pubmed/34124075 http://dx.doi.org/10.3389/fcell.2021.688885 Text en Copyright © 2021 Schorn, Dicke, Neugebauer, Schröter, Friedrich, Reuter and Ciarimboli. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Schorn, Sandra
Dicke, Ann-Kristin
Neugebauer, Ute
Schröter, Rita
Friedrich, Maren
Reuter, Stefan
Ciarimboli, Giuliano
Expression and Function of Organic Cation Transporter 2 in Pancreas
title Expression and Function of Organic Cation Transporter 2 in Pancreas
title_full Expression and Function of Organic Cation Transporter 2 in Pancreas
title_fullStr Expression and Function of Organic Cation Transporter 2 in Pancreas
title_full_unstemmed Expression and Function of Organic Cation Transporter 2 in Pancreas
title_short Expression and Function of Organic Cation Transporter 2 in Pancreas
title_sort expression and function of organic cation transporter 2 in pancreas
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195675/
https://www.ncbi.nlm.nih.gov/pubmed/34124075
http://dx.doi.org/10.3389/fcell.2021.688885
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