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Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus
BACKGROUND: Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using a rodent model. METHODS: Mice were treated with both nicotinami...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653899/ https://www.ncbi.nlm.nih.gov/pubmed/26594248 http://dx.doi.org/10.1186/s13098-015-0102-8 |
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author | Qiang, Shirong Nakatsu, Yusuke Seno, Yasuyuki Fujishiro, Midori Sakoda, Hideyuki Kushiyama, Akifumi Mori, Keiichi Matsunaga, Yasuka Yamamotoya, Takeshi Kamata, Hideaki Asano, Tomoichiro |
author_facet | Qiang, Shirong Nakatsu, Yusuke Seno, Yasuyuki Fujishiro, Midori Sakoda, Hideyuki Kushiyama, Akifumi Mori, Keiichi Matsunaga, Yasuka Yamamotoya, Takeshi Kamata, Hideaki Asano, Tomoichiro |
author_sort | Qiang, Shirong |
collection | PubMed |
description | BACKGROUND: Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using a rodent model. METHODS: Mice were treated with both nicotinamide and streptozotocin (NA/STZ) to reduce insulin secretory capacity, and then fed a high fat diet containing trans fatty acids (HFDT) for 8 weeks. The NA/STZ HFDT-fed mice were divided into two groups, either treated with luseogliflozin or untreated, during this period. The glucose elevations in the NA/STZ-treated and HFDT-fed mice were significantly improved by luseogliflozin administration. While HFDT feeding induced NASH development as shown by liver weight gain with lipid accumulation and increased serum alanine aminotransferase, these changes were all attenuated in the group treated with luseogliflozin. In addition, fibrotic change and increases in collagen deposition with upregulations of collagen1 and smooth muscle actin and inflammatory cytokine expressions observed in the HFDT-fed mouse livers were also normalized by luseogliflozin administration. CONCLUSIONS: Taken together, these results obtained in mice demonstrate the favorable effects of administering SGLT2 inhibitors, for the treatment of NASH associated with diabetes mellitus. We anticipate that these agents would be applicable to humans. |
format | Online Article Text |
id | pubmed-4653899 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46538992015-11-21 Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus Qiang, Shirong Nakatsu, Yusuke Seno, Yasuyuki Fujishiro, Midori Sakoda, Hideyuki Kushiyama, Akifumi Mori, Keiichi Matsunaga, Yasuka Yamamotoya, Takeshi Kamata, Hideaki Asano, Tomoichiro Diabetol Metab Syndr Short Report BACKGROUND: Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using a rodent model. METHODS: Mice were treated with both nicotinamide and streptozotocin (NA/STZ) to reduce insulin secretory capacity, and then fed a high fat diet containing trans fatty acids (HFDT) for 8 weeks. The NA/STZ HFDT-fed mice were divided into two groups, either treated with luseogliflozin or untreated, during this period. The glucose elevations in the NA/STZ-treated and HFDT-fed mice were significantly improved by luseogliflozin administration. While HFDT feeding induced NASH development as shown by liver weight gain with lipid accumulation and increased serum alanine aminotransferase, these changes were all attenuated in the group treated with luseogliflozin. In addition, fibrotic change and increases in collagen deposition with upregulations of collagen1 and smooth muscle actin and inflammatory cytokine expressions observed in the HFDT-fed mouse livers were also normalized by luseogliflozin administration. CONCLUSIONS: Taken together, these results obtained in mice demonstrate the favorable effects of administering SGLT2 inhibitors, for the treatment of NASH associated with diabetes mellitus. We anticipate that these agents would be applicable to humans. BioMed Central 2015-11-19 /pmc/articles/PMC4653899/ /pubmed/26594248 http://dx.doi.org/10.1186/s13098-015-0102-8 Text en © Qiang et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Short Report Qiang, Shirong Nakatsu, Yusuke Seno, Yasuyuki Fujishiro, Midori Sakoda, Hideyuki Kushiyama, Akifumi Mori, Keiichi Matsunaga, Yasuka Yamamotoya, Takeshi Kamata, Hideaki Asano, Tomoichiro Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title | Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title_full | Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title_fullStr | Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title_full_unstemmed | Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title_short | Treatment with the SGLT2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
title_sort | treatment with the sglt2 inhibitor luseogliflozin improves nonalcoholic steatohepatitis in a rodent model with diabetes mellitus |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4653899/ https://www.ncbi.nlm.nih.gov/pubmed/26594248 http://dx.doi.org/10.1186/s13098-015-0102-8 |
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