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Loss of EGR-1 uncouples compensatory responses of pancreatic β cells

Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, w...

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Autores principales: Leu, Sy-Ying, Kuo, Li-Hua, Weng, Wen-Tsan, Lien, I-Chia, Yang, Ching-Chun, Hsieh, Tai-Tzu, Cheng, Yi-Ning, Chien, Po-Hsiu, Ho, Li-Chun, Chen, Shun-Hua, Shan, Yan-Shen, Chen, Yun-Wen, Tsai, Pei-Jane, Sung, Junne-Ming, Tsai, Yau-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086362/
https://www.ncbi.nlm.nih.gov/pubmed/32226550
http://dx.doi.org/10.7150/thno.40664
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author Leu, Sy-Ying
Kuo, Li-Hua
Weng, Wen-Tsan
Lien, I-Chia
Yang, Ching-Chun
Hsieh, Tai-Tzu
Cheng, Yi-Ning
Chien, Po-Hsiu
Ho, Li-Chun
Chen, Shun-Hua
Shan, Yan-Shen
Chen, Yun-Wen
Tsai, Pei-Jane
Sung, Junne-Ming
Tsai, Yau-Sheng
author_facet Leu, Sy-Ying
Kuo, Li-Hua
Weng, Wen-Tsan
Lien, I-Chia
Yang, Ching-Chun
Hsieh, Tai-Tzu
Cheng, Yi-Ning
Chien, Po-Hsiu
Ho, Li-Chun
Chen, Shun-Hua
Shan, Yan-Shen
Chen, Yun-Wen
Tsai, Pei-Jane
Sung, Junne-Ming
Tsai, Yau-Sheng
author_sort Leu, Sy-Ying
collection PubMed
description Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that deficiency of EGR-1 might influence β-cell compensation in response to metabolic overload. Methods: Mice deficient in EGR-1 (Egr1(-/-)) were used to investigate the in vivo roles of EGR-1 in regulation of glucose homeostasis and beta-cell compensatory responses. Results: In response to a high-fat diet, Egr1(-/-) mice failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and attenuated hypertrophic response of islets. High-fat feeding caused a dramatic impairment in glucose-stimulated insulin secretion and downregulated the expression of genes encoding glucose sensing proteins. The cells co-expressing both insulin and glucagon were dramatically upregulated in islets of high-fat-fed Egr1(-/-) mice. EGR-1-deficient islets failed to maintain the transcriptional network for β-cell compensatory response. In human pancreatic tissues, EGR1 expression correlated with the expression of β-cell compensatory genes in the non-diabetic group, but not in the diabetic group. Conclusion: These results suggest that EGR-1 couples the transcriptional network to compensation for the loss of β-cell function and identity. Thus, our study highlights the early stress coupler EGR-1 as a critical factor in the development of pancreatic islet failure.
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spelling pubmed-70863622020-03-27 Loss of EGR-1 uncouples compensatory responses of pancreatic β cells Leu, Sy-Ying Kuo, Li-Hua Weng, Wen-Tsan Lien, I-Chia Yang, Ching-Chun Hsieh, Tai-Tzu Cheng, Yi-Ning Chien, Po-Hsiu Ho, Li-Chun Chen, Shun-Hua Shan, Yan-Shen Chen, Yun-Wen Tsai, Pei-Jane Sung, Junne-Ming Tsai, Yau-Sheng Theranostics Research Paper Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that deficiency of EGR-1 might influence β-cell compensation in response to metabolic overload. Methods: Mice deficient in EGR-1 (Egr1(-/-)) were used to investigate the in vivo roles of EGR-1 in regulation of glucose homeostasis and beta-cell compensatory responses. Results: In response to a high-fat diet, Egr1(-/-) mice failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and attenuated hypertrophic response of islets. High-fat feeding caused a dramatic impairment in glucose-stimulated insulin secretion and downregulated the expression of genes encoding glucose sensing proteins. The cells co-expressing both insulin and glucagon were dramatically upregulated in islets of high-fat-fed Egr1(-/-) mice. EGR-1-deficient islets failed to maintain the transcriptional network for β-cell compensatory response. In human pancreatic tissues, EGR1 expression correlated with the expression of β-cell compensatory genes in the non-diabetic group, but not in the diabetic group. Conclusion: These results suggest that EGR-1 couples the transcriptional network to compensation for the loss of β-cell function and identity. Thus, our study highlights the early stress coupler EGR-1 as a critical factor in the development of pancreatic islet failure. Ivyspring International Publisher 2020-03-04 /pmc/articles/PMC7086362/ /pubmed/32226550 http://dx.doi.org/10.7150/thno.40664 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Leu, Sy-Ying
Kuo, Li-Hua
Weng, Wen-Tsan
Lien, I-Chia
Yang, Ching-Chun
Hsieh, Tai-Tzu
Cheng, Yi-Ning
Chien, Po-Hsiu
Ho, Li-Chun
Chen, Shun-Hua
Shan, Yan-Shen
Chen, Yun-Wen
Tsai, Pei-Jane
Sung, Junne-Ming
Tsai, Yau-Sheng
Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title_full Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title_fullStr Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title_full_unstemmed Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title_short Loss of EGR-1 uncouples compensatory responses of pancreatic β cells
title_sort loss of egr-1 uncouples compensatory responses of pancreatic β cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086362/
https://www.ncbi.nlm.nih.gov/pubmed/32226550
http://dx.doi.org/10.7150/thno.40664
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