Involvement of AMPK activation in the inhibition of hepatic gluconeogenesis by Ficus carica leaf extract in diabetic mice and HepG2 cells - 09/12/18
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Graphical abstract |
AMP-activated protein kinase (AMPK) plays pivotal roles in insulin sensitivity and glucose homeostasis. PEPCK, G6pase, PGC-1α, FOXO1, HNF4α are the key enzymes and transcription factors in gluconeogenesis. PGC-1α, FOXO1, HNF4α can regulate G6Pase and PEPCK enzymes gene expression.
Highlights |
• | Ficus carica leaf (FCL) extract possesses hypoglycemic effects. |
• | FCL extract inhibited PEPCK and G6Pase expression in diabetic mice and cells. |
• | FCL extract activated AMPK and decreased the expressions of PGC-1α, HNF4α, and FOXO1. |
• | FCL extract inhibits hepatic gluconeogenesis via the activation of AMPK. |
Abstract |
The aim of this study was to explore the possible mechanisms of Ficus carica leaf (FCL) extract in suppressing hepatic gluconeogenesis in diabetic mice. Diabetic mice (streptozotocin-induced) received 1 g/kg of FCL extract twice a day for 6 weeks. Fasting blood glucose levels were measured and a 2-h oral glucose tolerance test was conducted. AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α) expression was examined. HepG2 hepatocytes were treated with FCL extract and an AMPK inhibitor (compound C) or agonist (AICAR), and PEPCK, G6pase, PGC-1α, AMPK, forkhead transcription factor O1 (FOXO1), and hepatic nuclear factor 4α (HNF4α) expression was determined. The results showed that FCL extract inhibited the expression of PEPCK and G6Pase in the liver of diabetic mice and HepG2 hepatocytes. FCL extract activated AMPK and decreased PGC-1α, HNF4α, and FOXO1 expression. The AMPK inhibitor attenuated those effects through inhibiting gluconeogenesis, while the AMPK agonist partially enhanced gluconeogenesis. In conclusion, FCL extract inhibits hepatic gluconeogenesis via activation of AMPK and down-regulation of gluconeogenic enzymes.
El texto completo de este artículo está disponible en PDF.Abbreviations : AMPK, DM, FBG, FBS, FCL, FOXO1, G6Pase, HNF4α, OGTT, PEPCK, PGC-1α, RT-PCR, SDS-PAGE, STZ, TC, TG
Keywords : Ficus carica, AMP-activated protein kinase, Diabetes mellitus, Gluconeogenesis, Phosphoenolpyruvate carboxykinase, Glucose-6-phosphatase
Esquema
Vol 109
P. 188-194 - janvier 2019 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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