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The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasti...

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Autores principales: Lertpatipanpong, Pattawika, Lee, Jaehak, Kim, Ilju, Eling, Thomas, Oh, Seung Yeon, Seong, Je Kyung, Baek, Seung Joon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298384/
https://www.ncbi.nlm.nih.gov/pubmed/34294853
http://dx.doi.org/10.1038/s41598-021-94581-y
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author Lertpatipanpong, Pattawika
Lee, Jaehak
Kim, Ilju
Eling, Thomas
Oh, Seung Yeon
Seong, Je Kyung
Baek, Seung Joon
author_facet Lertpatipanpong, Pattawika
Lee, Jaehak
Kim, Ilju
Eling, Thomas
Oh, Seung Yeon
Seong, Je Kyung
Baek, Seung Joon
author_sort Lertpatipanpong, Pattawika
collection PubMed
description Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.
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spelling pubmed-82983842021-07-23 The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice Lertpatipanpong, Pattawika Lee, Jaehak Kim, Ilju Eling, Thomas Oh, Seung Yeon Seong, Je Kyung Baek, Seung Joon Sci Rep Article Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice. Nature Publishing Group UK 2021-07-22 /pmc/articles/PMC8298384/ /pubmed/34294853 http://dx.doi.org/10.1038/s41598-021-94581-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lertpatipanpong, Pattawika
Lee, Jaehak
Kim, Ilju
Eling, Thomas
Oh, Seung Yeon
Seong, Je Kyung
Baek, Seung Joon
The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title_full The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title_fullStr The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title_full_unstemmed The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title_short The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice
title_sort anti-diabetic effects of nag-1/gdf15 on hfd/stz-induced mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298384/
https://www.ncbi.nlm.nih.gov/pubmed/34294853
http://dx.doi.org/10.1038/s41598-021-94581-y
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