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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.*

Regulation of guconeogenesis by aldo-keto-reductase 1a1b in zebrafish.

iScience 23:101763 (2020)
Publ. Version/Full Text Research data DOI PMC
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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 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Human Metabolism ; Molecular Genetics
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Journal iScience
Quellenangaben Volume: 23, Issue: 12, Pages: , Article Number: 101763 Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-501900-251
DOI 10.1016/j.isci.2020.101763
Scopus ID 85097063392
PubMed ID 33251496
Erfassungsdatum 2020-12-15
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