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Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells

OBJECTIVE: Altered gene expression contributes to the development of type 2 diabetes (T2D); thus, the analysis of differentially expressed genes between diabetes-susceptible and diabetes-resistant mouse models is an important tool for the determination of candidate genes that participate in the path...

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Autores principales: Gässler, Anneke, Quiclet, Charline, Kluth, Oliver, Gottmann, Pascal, Schwerbel, Kristin, Helms, Anett, Stadion, Mandy, Wilhelmi, Ilka, Jonas, Wenke, Ouni, Meriem, Mayer, Frank, Spranger, Joachim, Schürmann, Annette, Vogel, Heike
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365933/
https://www.ncbi.nlm.nih.gov/pubmed/32565358
http://dx.doi.org/10.1016/j.molmet.2020.101042
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author Gässler, Anneke
Quiclet, Charline
Kluth, Oliver
Gottmann, Pascal
Schwerbel, Kristin
Helms, Anett
Stadion, Mandy
Wilhelmi, Ilka
Jonas, Wenke
Ouni, Meriem
Mayer, Frank
Spranger, Joachim
Schürmann, Annette
Vogel, Heike
author_facet Gässler, Anneke
Quiclet, Charline
Kluth, Oliver
Gottmann, Pascal
Schwerbel, Kristin
Helms, Anett
Stadion, Mandy
Wilhelmi, Ilka
Jonas, Wenke
Ouni, Meriem
Mayer, Frank
Spranger, Joachim
Schürmann, Annette
Vogel, Heike
author_sort Gässler, Anneke
collection PubMed
description OBJECTIVE: Altered gene expression contributes to the development of type 2 diabetes (T2D); thus, the analysis of differentially expressed genes between diabetes-susceptible and diabetes-resistant mouse models is an important tool for the determination of candidate genes that participate in the pathology. Based on RNA-seq and array data comparing pancreatic gene expression of diabetes-prone New Zealand Obese (NZO) mice and diabetes-resistant B6.V-ob/ob (B6-ob/ob) mice, the gap junction protein beta 4 (Gjb4) was identified as a putative novel T2D candidate gene. METHODS: Gjb4 was overexpressed in primary islet cells derived from C57BL/6 (B6) mice and INS-1 cells via adenoviral-mediated infection. The proliferation rate of cells was assessed by BrdU incorporation, and insulin secretion was measured under low (2.8 mM) and high (20 mM) glucose concentration. INS-1 cell apoptosis rate was determined by Western blotting assessing cleaved caspase 3 levels. RESULTS: Overexpression of Gjb4 in primary islet cells significantly inhibited the proliferation by 47%, reduced insulin secretion of primary islets (46%) and INS-1 cells (51%), and enhanced the rate of apoptosis by 63% in INS-1 cells. Moreover, an altered expression of the miR-341-3p contributes to the Gjb4 expression difference between diabetes-prone and diabetes-resistant mice. CONCLUSIONS: The gap junction protein Gjb4 is highly expressed in islets of diabetes-prone NZO mice and may play a role in the development of T2D by altering islet cell function, inducing apoptosis and inhibiting proliferation.
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spelling pubmed-73659332020-07-20 Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells Gässler, Anneke Quiclet, Charline Kluth, Oliver Gottmann, Pascal Schwerbel, Kristin Helms, Anett Stadion, Mandy Wilhelmi, Ilka Jonas, Wenke Ouni, Meriem Mayer, Frank Spranger, Joachim Schürmann, Annette Vogel, Heike Mol Metab Brief Communication OBJECTIVE: Altered gene expression contributes to the development of type 2 diabetes (T2D); thus, the analysis of differentially expressed genes between diabetes-susceptible and diabetes-resistant mouse models is an important tool for the determination of candidate genes that participate in the pathology. Based on RNA-seq and array data comparing pancreatic gene expression of diabetes-prone New Zealand Obese (NZO) mice and diabetes-resistant B6.V-ob/ob (B6-ob/ob) mice, the gap junction protein beta 4 (Gjb4) was identified as a putative novel T2D candidate gene. METHODS: Gjb4 was overexpressed in primary islet cells derived from C57BL/6 (B6) mice and INS-1 cells via adenoviral-mediated infection. The proliferation rate of cells was assessed by BrdU incorporation, and insulin secretion was measured under low (2.8 mM) and high (20 mM) glucose concentration. INS-1 cell apoptosis rate was determined by Western blotting assessing cleaved caspase 3 levels. RESULTS: Overexpression of Gjb4 in primary islet cells significantly inhibited the proliferation by 47%, reduced insulin secretion of primary islets (46%) and INS-1 cells (51%), and enhanced the rate of apoptosis by 63% in INS-1 cells. Moreover, an altered expression of the miR-341-3p contributes to the Gjb4 expression difference between diabetes-prone and diabetes-resistant mice. CONCLUSIONS: The gap junction protein Gjb4 is highly expressed in islets of diabetes-prone NZO mice and may play a role in the development of T2D by altering islet cell function, inducing apoptosis and inhibiting proliferation. Elsevier 2020-06-18 /pmc/articles/PMC7365933/ /pubmed/32565358 http://dx.doi.org/10.1016/j.molmet.2020.101042 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Brief Communication
Gässler, Anneke
Quiclet, Charline
Kluth, Oliver
Gottmann, Pascal
Schwerbel, Kristin
Helms, Anett
Stadion, Mandy
Wilhelmi, Ilka
Jonas, Wenke
Ouni, Meriem
Mayer, Frank
Spranger, Joachim
Schürmann, Annette
Vogel, Heike
Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title_full Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title_fullStr Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title_full_unstemmed Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title_short Overexpression of Gjb4 impairs cell proliferation and insulin secretion in primary islet cells
title_sort overexpression of gjb4 impairs cell proliferation and insulin secretion in primary islet cells
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365933/
https://www.ncbi.nlm.nih.gov/pubmed/32565358
http://dx.doi.org/10.1016/j.molmet.2020.101042
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