Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis.
Animals
Blood Glucose
/ analysis
Carcinogenesis
/ drug effects
Carcinoma, Hepatocellular
/ prevention & control
Diabetes Mellitus, Experimental
/ chemically induced
Diet, High-Fat
/ adverse effects
Disease Models, Animal
Glucagon-Like Peptide-1 Receptor
/ agonists
Hypoglycemic Agents
/ administration & dosage
Insulin
/ blood
Liraglutide
/ administration & dosage
Liver Neoplasms
/ prevention & control
Male
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease
/ complications
Streptozocin
/ adverse effects
Treatment Outcome
NAFLD
NASH
ballooning
hepatocarcinogenesis
islet
liraglutide
liver cancer
prognosis
β-cell
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
10 Aug 2020
10 Aug 2020
Historique:
received:
31
05
2020
revised:
05
08
2020
accepted:
06
08
2020
entrez:
14
8
2020
pubmed:
14
8
2020
medline:
9
3
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32785012
pii: ijms21165722
doi: 10.3390/ijms21165722
pmc: PMC7460814
pii:
doi:
Substances chimiques
Blood Glucose
0
Glucagon-Like Peptide-1 Receptor
0
Hypoglycemic Agents
0
Insulin
0
Streptozocin
5W494URQ81
Liraglutide
839I73S42A
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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