Development and Validation of Type 2 Diabetic Zebrafish Model for Cell-Based Treatments

Arjmand, Babak; Alavi-Moghadam, Sepideh; Kokabi-Hamidpour, Shayesteh; Arjmand, Rasta; Rezaei‐Tavirani, Mostafa; Larijani, Bagher; Goodarzi, Parisa; Mehrdad, Neda; Rajaeinejad, Mohsen

doi:10.1007/7651_2022_475

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Multiple techniques have been developed to establish zebrafish diabetes models, including chemical methods, dietary induction, glucose soaking, and gene knockout [29]. The zebrafish model of diabetes is employed for investigating stem cell therapy for treating diabetes [30] and diabetic heart failure [31]. Dietary-induced diabetes leads to increased insulin secretion in the pancreases of zebrafish [23,32].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish

Ren

Song

et al. 2023

IJMS

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Diabetes has gradually become a serious disease that threatens human health. It can induce various complications, and the pathogenesis of diabetes is quite complex and not yet fully elucidated. The zebrafish has been widely acknowledged as a useful model for investigating the mechanisms underlying the pathogenesis and therapeutic interventions of diabetes. However, the molecular basis of zebrafish diabetes induced by overfeeding remains unknown. In this study, a zebrafish diabetes model was established by overfeeding, and the molecular basis of zebrafish diabetes induced by overfeeding was explored. Compared with the control group, the body length, body weight, and condition factor index of zebrafish increased significantly after four weeks of overfeeding. There was a significant elevation in the fasting blood glucose level, accompanied by a large number of lipid droplets accumulated within the liver. The levels of triglycerides and cholesterol in both the serum and liver exhibited a statistically significant increase. Transcriptome sequencing was employed to investigate changes in the livers of overfed zebrafish. The number of up-regulated and down-regulated differentially expressed genes (DEGs) was 1582 and 2404, respectively, in the livers of overfed zebrafish. The DEGs were subjected to KEGG and GO enrichment analyses, and the hub signaling pathways and hub DEGs were identified. The results demonstrate that sixteen genes within the signal pathway associated with fatty acid metabolism were found to be significantly up-regulated. Specifically, these genes were found to mainly participate in fatty acid transport, fatty acid oxidation, and ketogenesis. Furthermore, thirteen genes that play a crucial role in glucose metabolism, particularly in the pathways of glycolysis and glycogenesis, were significantly down-regulated in the livers of overfed zebrafish. These results indicate insulin resistance and inhibition of glucose entry into liver cells in the livers of overfed zebrafish. These findings elucidate the underlying molecular basis of zebrafish diabetes induced by overfeeding and provide a model for further investigation of the pathogenesis and therapeutics of diabetes.

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