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An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)

Background: Type 2 diabetes mellitus has recently been identified as a mediator of neurodegeneration. However, the molecular mechanisms have not been clearly elucidated. We aimed to investigate insulin resistance associated with neurodegenerative events in zebrafish larvae. Methods: Larvae aged 72 h...

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Main Authors: Md Razip, Nurliyana Najwa, Mohd Noor, Suzita, Norazit, Anwar, Nordin, Norshariza, Mohd Sakeh, Nurshafika, Khaza’ai, Huzwah
Format: Article
Published: Multidisciplinary Digital Publishing Institute 2022
Online Access:http://psasir.upm.edu.my/id/eprint/100227/
https://www.mdpi.com/1422-0067/23/15/8290
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spelling my.upm.eprints.1002272024-07-11T03:58:53Z http://psasir.upm.edu.my/id/eprint/100227/ An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio) Md Razip, Nurliyana Najwa Mohd Noor, Suzita Norazit, Anwar Nordin, Norshariza Mohd Sakeh, Nurshafika Khaza’ai, Huzwah Background: Type 2 diabetes mellitus has recently been identified as a mediator of neurodegeneration. However, the molecular mechanisms have not been clearly elucidated. We aimed to investigate insulin resistance associated with neurodegenerative events in zebrafish larvae. Methods: Larvae aged 72 h-post-fertilization (hpf) were induced to insulin resistance by immersion in 250 nM insulin and were then reinduced with 100 nM insulin at 96 hpf. This model was validated by a glucose levels assay, qPCR analysis of selected genes (akt, pepck, zglut3 and claudin-5a) and Oil Red-O (ORO) staining of the yolk sac for lipid distribution. The association of insulin resistance and neurodegeneration was validated by malondialdehyde (MDA), glutathione (GSH) assays, and by integrating next-generation sequencing with database for annotation, visualization and integrated discovery (DAVID). Results: There was a significant increase in glucose levels at 180 min in the insulin-resistant group. However, it decreased at 400 min after the re-challenge. Insulin-signaling mediators, akt and pepck, were showed significantly downregulated up to 400 min after insulin immersion (p < 0.05). Meanwhile, claudin-5a assessed blood–brain barrier (BBB) integrity and showed significant deterioration after 400 min of post-insulin immersion. ORO staining remarked the increase in yolk sac size in the insulin-resistant group. After the confirmation of insulin resistance, MDA levels increased significantly in the insulin-resistant group compared to the control group in the following parameters. Furthermore, dysregulated MAPK- and Wnt/Ca2+-signaling pathways were observed in the insulin-resistant group, disrupting energy metabolism and causing BBB injury. Conclusions: We conclude that the insulin-resistant zebrafish larvae alter the metabolic physiology associated with neurodegeneration. Multidisciplinary Digital Publishing Institute 2022-07-27 Article PeerReviewed Md Razip, Nurliyana Najwa and Mohd Noor, Suzita and Norazit, Anwar and Nordin, Norshariza and Mohd Sakeh, Nurshafika and Khaza’ai, Huzwah (2022) An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio). International Journal of Molecular Sciences, 23 (15). art. no. 8290. pp. 1-23. ISSN 1422-0067 https://www.mdpi.com/1422-0067/23/15/8290 10.3390/ijms23158290
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
description Background: Type 2 diabetes mellitus has recently been identified as a mediator of neurodegeneration. However, the molecular mechanisms have not been clearly elucidated. We aimed to investigate insulin resistance associated with neurodegenerative events in zebrafish larvae. Methods: Larvae aged 72 h-post-fertilization (hpf) were induced to insulin resistance by immersion in 250 nM insulin and were then reinduced with 100 nM insulin at 96 hpf. This model was validated by a glucose levels assay, qPCR analysis of selected genes (akt, pepck, zglut3 and claudin-5a) and Oil Red-O (ORO) staining of the yolk sac for lipid distribution. The association of insulin resistance and neurodegeneration was validated by malondialdehyde (MDA), glutathione (GSH) assays, and by integrating next-generation sequencing with database for annotation, visualization and integrated discovery (DAVID). Results: There was a significant increase in glucose levels at 180 min in the insulin-resistant group. However, it decreased at 400 min after the re-challenge. Insulin-signaling mediators, akt and pepck, were showed significantly downregulated up to 400 min after insulin immersion (p < 0.05). Meanwhile, claudin-5a assessed blood–brain barrier (BBB) integrity and showed significant deterioration after 400 min of post-insulin immersion. ORO staining remarked the increase in yolk sac size in the insulin-resistant group. After the confirmation of insulin resistance, MDA levels increased significantly in the insulin-resistant group compared to the control group in the following parameters. Furthermore, dysregulated MAPK- and Wnt/Ca2+-signaling pathways were observed in the insulin-resistant group, disrupting energy metabolism and causing BBB injury. Conclusions: We conclude that the insulin-resistant zebrafish larvae alter the metabolic physiology associated with neurodegeneration.
format Article
author Md Razip, Nurliyana Najwa
Mohd Noor, Suzita
Norazit, Anwar
Nordin, Norshariza
Mohd Sakeh, Nurshafika
Khaza’ai, Huzwah
spellingShingle Md Razip, Nurliyana Najwa
Mohd Noor, Suzita
Norazit, Anwar
Nordin, Norshariza
Mohd Sakeh, Nurshafika
Khaza’ai, Huzwah
An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
author_facet Md Razip, Nurliyana Najwa
Mohd Noor, Suzita
Norazit, Anwar
Nordin, Norshariza
Mohd Sakeh, Nurshafika
Khaza’ai, Huzwah
author_sort Md Razip, Nurliyana Najwa
title An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
title_short An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
title_full An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
title_fullStr An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
title_full_unstemmed An association between insulin resistance and neurodegeneration in zebrafish larval model (Danio rerio)
title_sort association between insulin resistance and neurodegeneration in zebrafish larval model (danio rerio)
publisher Multidisciplinary Digital Publishing Institute
publishDate 2022
url http://psasir.upm.edu.my/id/eprint/100227/
https://www.mdpi.com/1422-0067/23/15/8290
_version_ 1805889505355366400
score 13.211869

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