PUBLICATION
Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish
- Authors
- Li, X., Schmöhl, F., Qi, H., Bennewitz, K., Tabler, C.T., Poschet, G., Hell, R., Volk, N., Poth, T., Hausser, I., Morgenstern, J., Fleming, T., Nawroth, P.P., Kroll, J.
- ID
- ZDB-PUB-201201-4
- Date
- 2020
- Source
- iScience 23: 101763 (Journal)
- Registered Authors
- Kroll, Jens, Schmöhl, Felix
- Keywords
- Human Metabolism, Molecular Genetics
- MeSH Terms
- none
- PubMed
- 33251496 Full text @ iScience
Citation
Li, X., Schmöhl, F., Qi, H., Bennewitz, K., Tabler, C.T., Poschet, G., Hell, R., Volk, N., Poth, T., Hausser, I., Morgenstern, J., Fleming, T., Nawroth, P.P., Kroll, J. (2020) Regulation of Gluconeogenesis by Aldo-keto-reductase 1a1b in Zebrafish. iScience. 23:101763.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping