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Regulation of gluconeogenesis by Aldo-keto-reductase 1a1b in zebrafish

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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...

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Main Authors: Li, Xiaogang (Author) , Schmöhl, Felix (Author) , Qi, Haozhe (Author) , Bennewitz, Katrin (Author) , Tabler, Christoph Tobias (Author) , Poschet, Gernot (Author) , Hell, Rüdiger (Author) , Volk, Nadine (Author) , Poth, Tanja (Author) , Haußer-Siller, Ingrid (Author) , Morgenstern, Jakob (Author) , Fleming, Thomas (Author) , Nawroth, Peter Paul (Author) , Kroll, Jens (Author)
Format: Article (Journal)
Language:English
Published: December 18, 2020
In: iScience
Year: 2020, Volume: 23, Issue: 12
ISSN:2589-0042
DOI:10.1016/j.isci.2020.101763
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.isci.2020.101763
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2589004220309603
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Author Notes:Xiaogang Li, Felix Schmöhl, Haozhe Qi, Katrin Bennewitz, Christoph T. Tabler, Gernot Poschet, Rüdiger Hell, Nadine Volk, Tanja Poth, Ingrid Hausser, Jakob Morgenstern, Thomas Fleming, Peter Paul Nawroth, and Jens Kroll
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Summary: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.
Item Description:Gesehen am 22.02.2021
Physical Description:Online Resource
ISSN:2589-0042
DOI:10.1016/j.isci.2020.101763

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