PUBLICATION
Modulation of Redox and insulin signaling underlie the anti-hyperglycemic and antioxidant effects of diphenyl diselenide in zebrafish
- Authors
- Dos Santos, M.M., de Macedo, G.T., Prestes, A.S., Ecker, A., Müller, T.E., Leitemperger, J., Fontana, B.D., Ardisson-Araújo, D.M.P., Rosemberg, D.B., Barbosa, N.V.
- ID
- ZDB-PUB-200617-22
- Date
- 2020
- Source
- Free radical biology & medicine 158: 20-31 (Journal)
- Registered Authors
- Keywords
- Hyperglycemia, diabetes, diphenyl diselenide, insulin signaling, oxidative stress, zebrafish
- MeSH Terms
-
- Animals
- Antioxidants*/pharmacology
- Benzene Derivatives
- Hypoglycemic Agents
- Insulin
- Organoselenium Compounds
- Oxidation-Reduction
- Oxidative Stress
- Signal Transduction
- Zebrafish*
- PubMed
- 32544425 Full text @ Free Radic. Biol. Med.
Citation
Dos Santos, M.M., de Macedo, G.T., Prestes, A.S., Ecker, A., Müller, T.E., Leitemperger, J., Fontana, B.D., Ardisson-Araújo, D.M.P., Rosemberg, D.B., Barbosa, N.V. (2020) Modulation of Redox and insulin signaling underlie the anti-hyperglycemic and antioxidant effects of diphenyl diselenide in zebrafish. Free radical biology & medicine. 158:20-31.
Abstract
The organic selenium compound diphenyl diselenide (DD) has been recognized as an antioxidant and neuroprotective agent, exerting an anti-hyperglycemic effect in experimental models of diabetes. However, the precise mechanisms involved in the protection are unclear. Using the zebrafish (Danio rerio) as a model organism, here we investigated biomarkers underlying the protective effects of DD against hyperglycemia, targeting in a transcriptional approach the redox and insulin-signaling pathway. Fish were fed on a diet containing DD (3 mg/kg) for 74 days. In the last 14 days, they were exposed to a 111 mM glucose solution to induce a hyperglycemic state. DD reduced blood glucose levels as well as normalized the brain mRNA transcription of four insulin receptors-coding genes (Insra1, Insra2, Insrb1, Insrb2), which were down-regulated by glucose. DD alone caused an up-regulation of relative mRNA transcription in both Insra receptors and glucose transporter 3 genes. DD counteracted hyperglycemia-induced lipid peroxidation, protein and thiol depletion. Along with the decreased activity of antioxidant enzymes SOD and GPx, the brain of hyperglycemic fish presented a reduction in mRNA transcription of FoxO3A, FoxO3B, Nrf2, GPx3A, SOD1, and SOD2 genes. Besides normalizing the transcriptional levels, DD caused an up-regulation of relative mRNAs that encode Nrf2, FoxO1A, FOXO3A, GPx4A, PTP1B, AKT and SelP. Collectively, our findings suggest that the antioxidant and anti-hyperglycemic actions of DD in a zebrafish diabetes model are likely associated with the regulation of the oxidative stress resistance and the insulin-signaling pathway and that could be related to the modulation at mRNA level of two important transcription factors, Nrf2 and FoxO.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping