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Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity

Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secret...

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Autores principales: Chen, Sing-Young, Olzomer, Ellen M., Beretta, Martina, Cantley, James, Nunemaker, Craig S., Hoehn, Kyle L., Byrne, Frances L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456207/
https://www.ncbi.nlm.nih.gov/pubmed/36077188
http://dx.doi.org/10.3390/ijms23179798
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author Chen, Sing-Young
Olzomer, Ellen M.
Beretta, Martina
Cantley, James
Nunemaker, Craig S.
Hoehn, Kyle L.
Byrne, Frances L.
author_facet Chen, Sing-Young
Olzomer, Ellen M.
Beretta, Martina
Cantley, James
Nunemaker, Craig S.
Hoehn, Kyle L.
Byrne, Frances L.
author_sort Chen, Sing-Young
collection PubMed
description Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secretion in human islets, while GLUT2 is the key isoform in rodent islets. However, it is unclear whether other glucose transporters also contribute to insulin secretion by pancreatic islets. Herein, we show that SLC2A6 (GLUT6) is markedly upregulated in pancreatic islets from genetically obese leptin-mutant (ob/ob) and leptin receptor-mutant (db/db) mice, compared to lean controls. Furthermore, we observe that islet SLC2A6 expression positively correlates with body mass index in human patients with type 2 diabetes. To investigate whether GLUT6 plays a functional role in islets, we crossed GLUT6 knockout mice with C57BL/6 ob/ob mice. Pancreatic islets isolated from ob/ob mice lacking GLUT6 secreted more insulin in response to high-dose glucose, compared to ob/ob mice that were wild type for GLUT6. The loss of GLUT6 in ob/ob mice had no adverse impact on body mass, body composition, or glucose tolerance at a whole-body level. This study demonstrates that GLUT6 plays a role in pancreatic islet insulin secretion in vitro but is not a dominant glucose transporter that alters whole-body metabolic physiology in ob/ob mice.
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spelling pubmed-94562072022-09-09 Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity Chen, Sing-Young Olzomer, Ellen M. Beretta, Martina Cantley, James Nunemaker, Craig S. Hoehn, Kyle L. Byrne, Frances L. Int J Mol Sci Article Obesity-related insulin resistance is a highly prevalent and growing health concern, which places stress on the pancreatic islets of Langerhans by increasing insulin secretion to lower blood glucose levels. The glucose transporters GLUT1 and GLUT3 play a key role in glucose-stimulated insulin secretion in human islets, while GLUT2 is the key isoform in rodent islets. However, it is unclear whether other glucose transporters also contribute to insulin secretion by pancreatic islets. Herein, we show that SLC2A6 (GLUT6) is markedly upregulated in pancreatic islets from genetically obese leptin-mutant (ob/ob) and leptin receptor-mutant (db/db) mice, compared to lean controls. Furthermore, we observe that islet SLC2A6 expression positively correlates with body mass index in human patients with type 2 diabetes. To investigate whether GLUT6 plays a functional role in islets, we crossed GLUT6 knockout mice with C57BL/6 ob/ob mice. Pancreatic islets isolated from ob/ob mice lacking GLUT6 secreted more insulin in response to high-dose glucose, compared to ob/ob mice that were wild type for GLUT6. The loss of GLUT6 in ob/ob mice had no adverse impact on body mass, body composition, or glucose tolerance at a whole-body level. This study demonstrates that GLUT6 plays a role in pancreatic islet insulin secretion in vitro but is not a dominant glucose transporter that alters whole-body metabolic physiology in ob/ob mice. MDPI 2022-08-29 /pmc/articles/PMC9456207/ /pubmed/36077188 http://dx.doi.org/10.3390/ijms23179798 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Sing-Young
Olzomer, Ellen M.
Beretta, Martina
Cantley, James
Nunemaker, Craig S.
Hoehn, Kyle L.
Byrne, Frances L.
Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title_full Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title_fullStr Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title_full_unstemmed Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title_short Investigating the Expression and Function of the Glucose Transporter GLUT6 in Obesity
title_sort investigating the expression and function of the glucose transporter glut6 in obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456207/
https://www.ncbi.nlm.nih.gov/pubmed/36077188
http://dx.doi.org/10.3390/ijms23179798
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