Academic Journal
Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish
| العنوان: | Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish |
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| المؤلفون: | 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, Jens Kroll |
| المصدر: | iScience, Vol 23, Iss 12, Pp 101763- (2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Science |
| مصطلحات موضوعية: | Human Metabolism, Molecular Genetics, Science |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2589-0042 27415481 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2589004220309603; https://doaj.org/toc/2589-0042 |
| DOI: | 10.1016/j.isci.2020.101763 |
| URL الوصول: | https://doaj.org/article/8038c2712d2741548133c7a0daabb4b8 |
| رقم الانضمام: | edsdoj.8038c2712d2741548133c7a0daabb4b8 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 25890042 27415481 |
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| DOI: | 10.1016/j.isci.2020.101763 |