Cargando…
Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis
Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced diabetes and NASH were subcu...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460814/ https://www.ncbi.nlm.nih.gov/pubmed/32785012 http://dx.doi.org/10.3390/ijms21165722 |
_version_ | 1783576682950557696 |
---|---|
author | Kojima, Motoyasu Takahashi, Hirokazu Kuwashiro, Takuya Tanaka, Kenichi Mori, Hitoe Ozaki, Iwata Kitajima, Yoichiro Matsuda, Yayoi Ashida, Kenji Eguchi, Yuichiro Anzai, Keizo |
author_facet | Kojima, Motoyasu Takahashi, Hirokazu Kuwashiro, Takuya Tanaka, Kenichi Mori, Hitoe Ozaki, Iwata Kitajima, Yoichiro Matsuda, Yayoi Ashida, Kenji Eguchi, Yuichiro Anzai, Keizo |
author_sort | Kojima, Motoyasu |
collection | PubMed |
description | Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced diabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks. Glycemic control, hepatocarcinogenesis, and liver histology were compared between the groups. Fasting blood glucose levels were significantly lower in the liraglutide group than in the control group (210.0 ± 17.3 mg/dL vs. 601.8 ± 123.6 mg/dL), and fasting insulin levels were significantly increased by liraglutide (0.18 ± 0.06 ng/mL vs. 0.09 ± 0.03 ng/mL). Liraglutide completely suppressed hepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 ± 3.87; average tumor size, 8.1 ± 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and hepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and insulin-positive β-cells were observed in the pancreas in liraglutide-treated mice but not in control mice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic mice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes. |
format | Online Article Text |
id | pubmed-7460814 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74608142020-09-03 Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis Kojima, Motoyasu Takahashi, Hirokazu Kuwashiro, Takuya Tanaka, Kenichi Mori, Hitoe Ozaki, Iwata Kitajima, Yoichiro Matsuda, Yayoi Ashida, Kenji Eguchi, Yuichiro Anzai, Keizo Int J Mol Sci Article Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced diabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks. Glycemic control, hepatocarcinogenesis, and liver histology were compared between the groups. Fasting blood glucose levels were significantly lower in the liraglutide group than in the control group (210.0 ± 17.3 mg/dL vs. 601.8 ± 123.6 mg/dL), and fasting insulin levels were significantly increased by liraglutide (0.18 ± 0.06 ng/mL vs. 0.09 ± 0.03 ng/mL). Liraglutide completely suppressed hepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 ± 3.87; average tumor size, 8.1 ± 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and hepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and insulin-positive β-cells were observed in the pancreas in liraglutide-treated mice but not in control mice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic mice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes. MDPI 2020-08-10 /pmc/articles/PMC7460814/ /pubmed/32785012 http://dx.doi.org/10.3390/ijms21165722 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kojima, Motoyasu Takahashi, Hirokazu Kuwashiro, Takuya Tanaka, Kenichi Mori, Hitoe Ozaki, Iwata Kitajima, Yoichiro Matsuda, Yayoi Ashida, Kenji Eguchi, Yuichiro Anzai, Keizo Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title_full | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title_fullStr | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title_full_unstemmed | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title_short | Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis |
title_sort | glucagon-like peptide-1 receptor agonist prevented the progression of hepatocellular carcinoma in a mouse model of nonalcoholic steatohepatitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460814/ https://www.ncbi.nlm.nih.gov/pubmed/32785012 http://dx.doi.org/10.3390/ijms21165722 |
work_keys_str_mv | AT kojimamotoyasu glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT takahashihirokazu glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT kuwashirotakuya glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT tanakakenichi glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT morihitoe glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT ozakiiwata glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT kitajimayoichiro glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT matsudayayoi glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT ashidakenji glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT eguchiyuichiro glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis AT anzaikeizo glucagonlikepeptide1receptoragonistpreventedtheprogressionofhepatocellularcarcinomainamousemodelofnonalcoholicsteatohepatitis |