Baicalin ameliorates hepatic insulin resistance and gluconeogenic activity through inhibition of p38 MAPK/PGC-1α pathway.
Adipocytes
/ drug effects
Animals
Diet, High-Fat
/ adverse effects
Flavonoids
/ pharmacology
Gene Expression Regulation
/ drug effects
Gluconeogenesis
/ drug effects
Glucose Intolerance
/ drug therapy
Hepatocytes
/ drug effects
Insulin Resistance
Liver
/ drug effects
Male
Metformin
/ pharmacology
Mice, Inbred C57BL
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
/ antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases
/ antagonists & inhibitors
Baicalin
Gluconeogenesis
Hyperglycemia
PGC-1α
p38 MAPK
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
18
11
2018
revised:
18
08
2019
accepted:
22
08
2019
pubmed:
2
9
2019
medline:
13
2
2020
entrez:
2
9
2019
Statut:
ppublish
Résumé
Although the results of our and other studies show that baicalin can enhance glucose uptake and insulin sensitivity in skeletal muscle and adipocytes of mice, the specific metabolic contribution of baicalin on hepatic insulin resistance and gluconeogenic activity is still unclear. The aim of this study is to investigate whether baicalin is involved in regulation of hepatic insulin resistance and gluconeogenic activity and its underlying mechanisms. In the present study, high-fat diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 consecutive days, and hepatocytes were treated with baicalin (100 μM) or metformin (100 μM) in the presence of glucagon (200 nM) for 12 h. Then insulin resistance indexes and genes related to gluconeogenesis were examined in liver tissues. The present findings showed that baicalin decreased body weight, HOMA-IR, and alleviated high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Furthermore, baicalin markedly suppressed p-p38 MAPK, p-CREB, FoxO1, PGC-1α, PEPCK and G6Pase expression in liver of obese mice and hepatocytes. Moreover, inhibition of gluconeogenic genes by baicalin was also strengthened by p38MAPK inhibitor in hepatocytes. Baicalin suppressed expression of PGC-1α and gluconeogenic genes, and reduced glucose production in high-fat diet-induced obese mice. Baicalin ameliorated hepatic insulin resistance and gluconeogenic activity mainly through inhibition of p38 MAPK/PGC-1α signal pathway. This study provides a possibility of using baicalin to treat hyperglycemia and hepatic insulin resistance in clinic.
Sections du résumé
BACKGROUND
BACKGROUND
Although the results of our and other studies show that baicalin can enhance glucose uptake and insulin sensitivity in skeletal muscle and adipocytes of mice, the specific metabolic contribution of baicalin on hepatic insulin resistance and gluconeogenic activity is still unclear.
PURPOSE
OBJECTIVE
The aim of this study is to investigate whether baicalin is involved in regulation of hepatic insulin resistance and gluconeogenic activity and its underlying mechanisms.
STUDY DESIGN/METHODS
METHODS
In the present study, high-fat diet-induced obese mice were given 50 mg/kg baicalin intraperitoneally (i.p.) once a day for 21 consecutive days, and hepatocytes were treated with baicalin (100 μM) or metformin (100 μM) in the presence of glucagon (200 nM) for 12 h. Then insulin resistance indexes and genes related to gluconeogenesis were examined in liver tissues.
RESULTS
RESULTS
The present findings showed that baicalin decreased body weight, HOMA-IR, and alleviated high fat diet-induced glucose intolerance, hyperglycemia and insulin resistance in diet-induced obese mice. Furthermore, baicalin markedly suppressed p-p38 MAPK, p-CREB, FoxO1, PGC-1α, PEPCK and G6Pase expression in liver of obese mice and hepatocytes. Moreover, inhibition of gluconeogenic genes by baicalin was also strengthened by p38MAPK inhibitor in hepatocytes.
CONCLUSION
CONCLUSIONS
Baicalin suppressed expression of PGC-1α and gluconeogenic genes, and reduced glucose production in high-fat diet-induced obese mice. Baicalin ameliorated hepatic insulin resistance and gluconeogenic activity mainly through inhibition of p38 MAPK/PGC-1α signal pathway. This study provides a possibility of using baicalin to treat hyperglycemia and hepatic insulin resistance in clinic.
Identifiants
pubmed: 31473580
pii: S0944-7113(19)30239-9
doi: 10.1016/j.phymed.2019.153074
pii:
doi:
Substances chimiques
Flavonoids
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Ppargc1a protein, mouse
0
baicalin
347Q89U4M5
Metformin
9100L32L2N
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153074Informations de copyright
Copyright © 2019 Elsevier GmbH. All rights reserved.