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VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress

Vesicular monoamine transporter 2 (VMAT2) uptakes cytoplasmic monoamines into vesicles for storage. VMAT2 plays a role in modulating insulin release by regulating dopamine levels in the pancreas, although the exact mechanism remains elusive. We found that VMAT2 expression in β-cells specifically inc...

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Autores principales: Sakano, Daisuke, Uefune, Fumiya, Tokuma, Hiraku, Sonoda, Yuki, Matsuura, Kumi, Takeda, Naoki, Nakagata, Naomi, Kume, Kazuhiko, Shiraki, Nobuaki, Kume, Shoen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576560/
https://www.ncbi.nlm.nih.gov/pubmed/32826296
http://dx.doi.org/10.2337/db20-0207
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author Sakano, Daisuke
Uefune, Fumiya
Tokuma, Hiraku
Sonoda, Yuki
Matsuura, Kumi
Takeda, Naoki
Nakagata, Naomi
Kume, Kazuhiko
Shiraki, Nobuaki
Kume, Shoen
author_facet Sakano, Daisuke
Uefune, Fumiya
Tokuma, Hiraku
Sonoda, Yuki
Matsuura, Kumi
Takeda, Naoki
Nakagata, Naomi
Kume, Kazuhiko
Shiraki, Nobuaki
Kume, Shoen
author_sort Sakano, Daisuke
collection PubMed
description Vesicular monoamine transporter 2 (VMAT2) uptakes cytoplasmic monoamines into vesicles for storage. VMAT2 plays a role in modulating insulin release by regulating dopamine levels in the pancreas, although the exact mechanism remains elusive. We found that VMAT2 expression in β-cells specifically increases under high blood glucose conditions. The islets isolated from β-cell–specific Vmat2 knockout (βVmat2KO) mice show elevated insulin secretion levels in response to glucose stimulation. Under prolonged high-fat diet feedings, the βVmat2KO mice exhibit impaired glucose and insulin tolerance and progressive β-cell dysfunction. Here we demonstrate VMAT2 uptake of dopamine to protect dopamine from degradation by monoamine oxidase, thereby safeguarding β-cells from excess reactive oxygen species (ROS) exposure. In the context of high demand for insulin secretion, the absence of VMAT2 leads to elevated ROS in β-cells, which accelerates β-cell dedifferentiation and β-cell loss. Therefore, VMAT2 controls the amount of dopamine in β-cells, thereby protecting pancreatic β-cells from excessive oxidative stress.
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spelling pubmed-75765602020-11-02 VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress Sakano, Daisuke Uefune, Fumiya Tokuma, Hiraku Sonoda, Yuki Matsuura, Kumi Takeda, Naoki Nakagata, Naomi Kume, Kazuhiko Shiraki, Nobuaki Kume, Shoen Diabetes Islet Studies Vesicular monoamine transporter 2 (VMAT2) uptakes cytoplasmic monoamines into vesicles for storage. VMAT2 plays a role in modulating insulin release by regulating dopamine levels in the pancreas, although the exact mechanism remains elusive. We found that VMAT2 expression in β-cells specifically increases under high blood glucose conditions. The islets isolated from β-cell–specific Vmat2 knockout (βVmat2KO) mice show elevated insulin secretion levels in response to glucose stimulation. Under prolonged high-fat diet feedings, the βVmat2KO mice exhibit impaired glucose and insulin tolerance and progressive β-cell dysfunction. Here we demonstrate VMAT2 uptake of dopamine to protect dopamine from degradation by monoamine oxidase, thereby safeguarding β-cells from excess reactive oxygen species (ROS) exposure. In the context of high demand for insulin secretion, the absence of VMAT2 leads to elevated ROS in β-cells, which accelerates β-cell dedifferentiation and β-cell loss. Therefore, VMAT2 controls the amount of dopamine in β-cells, thereby protecting pancreatic β-cells from excessive oxidative stress. American Diabetes Association 2020-11 2020-08-21 /pmc/articles/PMC7576560/ /pubmed/32826296 http://dx.doi.org/10.2337/db20-0207 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.
spellingShingle Islet Studies
Sakano, Daisuke
Uefune, Fumiya
Tokuma, Hiraku
Sonoda, Yuki
Matsuura, Kumi
Takeda, Naoki
Nakagata, Naomi
Kume, Kazuhiko
Shiraki, Nobuaki
Kume, Shoen
VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title_full VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title_fullStr VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title_full_unstemmed VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title_short VMAT2 Safeguards β-Cells Against Dopamine Cytotoxicity Under High-Fat Diet–Induced Stress
title_sort vmat2 safeguards β-cells against dopamine cytotoxicity under high-fat diet–induced stress
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576560/
https://www.ncbi.nlm.nih.gov/pubmed/32826296
http://dx.doi.org/10.2337/db20-0207
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