PUBLICATION

Development of a Zebrafish Larvae Model for Diabetic Heart Failure With Reduced Ejection Fraction

Authors
Kim, I., Seok, S.H., Lee, H.Y.
ID
ZDB-PUB-230111-11
Date
2023
Source
Korean circulation journal   53: 344634-46 (Journal)
Registered Authors
Keywords
Diabetes mellitus, Heart failure, Zebrafish
MeSH Terms
none
PubMed
36627738 Full text @ Korean Circ J
Abstract
Background and objectives Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF.
Methods DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated.
Results The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed.
Conclusions We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
sc1Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocinDays 7-13
sc1Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocinDays 7-13
sc1Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocinDays 7-13
sc1Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocinDays 7-13
twu34Tgchemical treatment by environment: TerfenadineDays 7-13
twu34Tgchemical treatment by environment: TerfenadineDays 7-13
twu34Tgchemical treatment by environment: TerfenadineDays 7-13
twu34Tgchemical treatment by environment: TerfenadineDays 7-13
twu34Tgchemical treatment by environment: TerfenadineDays 7-13
twu34Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocin, chemical treatment by environment: TerfenadineDays 7-13
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
sc1TgTransgenic Insertion
    twu34TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      Human Disease Fish Conditions Evidence
      congestive heart failuretwu34Tgchemical treatment by environment: TerfenadineTAS
      diabetes mellitussc1Tgchemical treatment by environment: glucose, chemical treatment by environment: streptozocinTAS
      1 - 2 of 2
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      Sequence Targeting Reagents
      No data available
      Fish
      Fish
      sc1Tg
      twu34Tg
      1 - 2 of 2
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      Antibodies
      No data available
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
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      Mapping
      No data available
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      Citation
      Kim, I., Seok, S.H., Lee, H.Y. (2023) Development of a Zebrafish Larvae Model for Diabetic Heart Failure With Reduced Ejection Fraction. Korean circulation journal. 53:344634-46.