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Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish
Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of glucon...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683270/ https://www.ncbi.nlm.nih.gov/pubmed/33251496 http://dx.doi.org/10.1016/j.isci.2020.101763 |
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author | Li, Xiaogang Schmöhl, Felix Qi, Haozhe Bennewitz, Katrin Tabler, Christoph T. Poschet, Gernot Hell, Rüdiger Volk, Nadine Poth, Tanja Hausser, Ingrid Morgenstern, Jakob Fleming, Thomas Nawroth, Peter Paul Kroll, Jens |
author_facet | Li, Xiaogang Schmöhl, Felix Qi, Haozhe Bennewitz, Katrin Tabler, Christoph T. Poschet, Gernot Hell, Rüdiger Volk, Nadine Poth, Tanja Hausser, Ingrid Morgenstern, Jakob Fleming, Thomas Nawroth, Peter Paul Kroll, Jens |
author_sort | Li, Xiaogang |
collection | PubMed |
description | Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b(−/−) mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b(−/−) embryos. Akr1a1b(−/−) mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b(−/−) mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis. |
format | Online Article Text |
id | pubmed-7683270 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-76832702020-11-27 Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish Li, Xiaogang Schmöhl, Felix Qi, Haozhe Bennewitz, Katrin Tabler, Christoph T. Poschet, Gernot Hell, Rüdiger Volk, Nadine Poth, Tanja Hausser, Ingrid Morgenstern, Jakob Fleming, Thomas Nawroth, Peter Paul Kroll, Jens iScience Article Regulation of glucose homeostasis is a fundamental process to maintain blood glucose at a physiological level, and its dysregulation is associated with the development of several metabolic diseases. Here, we report on a zebrafish mutant for Aldo-keto-reductase 1a1b (akr1a1b) as a regulator of gluconeogenesis. Adult akr1a1b(−/−) mutant zebrafish developed fasting hypoglycemia, which was caused by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression as rate-limiting enzyme of gluconeogenesis. Subsequently, glucogenic amino acid glutamate as substrate for gluconeogenesis accumulated in the kidneys, but not in livers, and induced structural and functional pronephros alterations in 48-hpf akr1a1b(−/−) embryos. Akr1a1b(−/−) mutants displayed increased nitrosative stress as indicated by increased nitrotyrosine, and increased protein-S-nitrosylation. Inhibition of nitrosative stress using the NO synthase inhibitor L-NAME prevented kidney damage and normalized PEPCK expression in akr1a1b(−/−) mutants. Thus, the data have identified Akr1a1b as a regulator of gluconeogenesis in zebrafish and thereby controlling glucose homeostasis. Elsevier 2020-11-03 /pmc/articles/PMC7683270/ /pubmed/33251496 http://dx.doi.org/10.1016/j.isci.2020.101763 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 | Article Li, Xiaogang Schmöhl, Felix Qi, Haozhe Bennewitz, Katrin Tabler, Christoph T. Poschet, Gernot Hell, Rüdiger Volk, Nadine Poth, Tanja Hausser, Ingrid Morgenstern, Jakob Fleming, Thomas Nawroth, Peter Paul Kroll, Jens Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title_full | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title_fullStr | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title_full_unstemmed | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title_short | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
title_sort | regulation of gluconeogenesis by aldo-keto-reductase 1a1b in zebrafish |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683270/ https://www.ncbi.nlm.nih.gov/pubmed/33251496 http://dx.doi.org/10.1016/j.isci.2020.101763 |
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