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Published on: May 5, 2021
Characteristics of the New Insulin-Resistant Zebrafish Model
Youn Hee Nam1, Isabel Rodriguez1, Sung Woo Shin1
1Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin 17104, Gyeonggi, Korea.
Abstract:
Insulin resistance, which occurs when insulin levels are sufficiently high over a prolonged period, causing the cells to fail to respond normally to the hormone. As a system for insulin resistance and diabetes drug development, insulin-resistant rodent models have been clearly established, but there is a limitation to high-throughput drug screening. Recently, zebrafish have been identified as an excellent system for drug discovery and identification of therapeutic targets, but studies on insulin resistance models have not been extensively performed. Therefore, we aimed to make a rapid insulin-resistant zebrafish model that complements the existing rodent models. To establish this model, zebrafish were treated with 10 μM insulin for 48 h. This model showed characteristics of insulin-resistant disease such as damaged pancreatic islets. Then we confirmed the recovery of the pancreatic islets after pioglitazone treatment. In addition, it was found that insulin-resistant drugs have as significant an effect in zebrafish as in humans, and these results proved the value of the zebrafish insulin resistance model for drug selection. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that insulin resistance altered gene expression due to the MAPK signaling and calcium signaling pathways. This model demonstrates the utility of the zebrafish model for drug testing and drug discovery in insulin resistance and diabetes.
Insights
Researchers developed a rapid zebrafish model for insulin resistance, showing damaged pancreatic islets and drug recovery. This model proves valuable for high-throughput screening in diabetes drug discovery.
Area of Science:
- Endocrinology
- Pharmacology
- Genomics
Background:
- Insulin resistance, characterized by prolonged high insulin levels leading to cellular non-responsiveness, is a key factor in diabetes.
- Existing rodent models for insulin resistance and diabetes drug development lack high-throughput screening capabilities.
- Zebrafish offer a promising system for drug discovery, but robust insulin resistance models are underdeveloped.
Purpose of the Study:
- To establish a rapid and effective zebrafish model for insulin resistance.
- To complement existing rodent models for high-throughput drug screening.
- To investigate the therapeutic potential of drugs and elucidate underlying mechanisms in insulin resistance.
Main Methods:
- Zebrafish were induced into an insulin-resistant state by treatment with 10 μM insulin for 48 hours.
- Histological examination assessed pancreatic islet damage, and drug efficacy was evaluated using pioglitazone.
- RNA sequencing and KEGG pathway enrichment analysis identified molecular pathways affected by insulin resistance.
Main Results:
- The induced zebrafish model exhibited characteristics of insulin resistance, including pancreatic islet damage.
- Pioglitazone treatment successfully restored pancreatic islet integrity, demonstrating drug efficacy.
- Differential gene expression analysis revealed alterations in MAPK and calcium signaling pathways.
Conclusions:
- The developed zebrafish model effectively mimics human insulin resistance and is suitable for drug testing.
- This model validates the utility of zebrafish for high-throughput screening and drug discovery in diabetes.
- The study highlights the role of MAPK and calcium signaling in insulin resistance.
