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.

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Sensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.

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The EtOAc, n-BuOH, and aqueous fractions from the aerial parts of Malva verticillata have been shown to promote significant recovery from alloxan-induced pancreatic islet (PI) damage in zebrafish larvae at 10 μg/mL. Therefore, this study aimed to identify the principal active components of these plant parts and their pharmacological properties. Repeated SiO 2 and octadecyl SiO 2 column chromatography with the aerial parts of M. verticillata led to isolation of four phenolic compounds; these compounds were identified as benzyl--D-galactopyranoside (1), (-)-secoisolariciresinol-9′-O--D-glucopyranoside (2), transferulic acid (3), and trans-ferulic acid methyl ester (4) on the basis of physicochemical and spectroscopic analyses including infrared, nuclear magnetic resonance, and fast atom bombardment-mass spectroscopy. Compounds 1-4 were first isolated from M. verticillata in this study. Furthermore, compounds 1-4 recovered alloxan-induced PI damage in zebrafish. Especially, compound 3 recovered the size of the injured PIs by 83.8% (p=0.0007) compared to the alloxaninduced group, while compound 4 by 33.4% (p=0.0072). It is the first report that trans-ferulic acid (3) exhibited the protective effect on zebrafish larvae PIs damaged by alloxan.