1 research outputs found
Beneficial Effect of Betulinic Acid on Hyperglycemia via Suppression of Hepatic Glucose Production
The inhibitory effect of betulinic
acid (BA) on hepatic glucose
production was examined in HepG2 cells and high fat diet (HFD)-fed
ICR mice. BA significantly inhibited the hepatic glucose production
(HGP) and gene expression levels of PGC-1α, PEPCK, and G6Pase.
BA activated AMPK and suppressed the expression level of phosphorylated
CREB. These effects were all abolished in the presence of compound
C (an AMPK inhibitor). Moreover, inhibition of AMPK by overexpression
of dominant negative AMPK prevented BA from suppression of HGP, indicating
that the inhibitory effect of BA on HGP is AMPK-dependent. In addition,
BA markedly phosphorylated CAMKK, and phosphorylation of AMPK and
ACC, and suppression of HGP were all reversed in the presence of STO-609
(a CAMKK inhibitor), suggesting that CAMKK is an upstream kinase for
AMPK. In an animal study, HFD-fed ICR mice were orally administered
with 5 or 10 mg of BA per kg (B5 and B10) for three weeks. Plasma
glucose, triglyceride, and the insulin resistance index of the B10
group were decreased by 34%, 59%, and 38%, respectively. In a pyruvate
tolerance test, pyruvate-induced glucose excursion was decreased by
27% when mice were pretreated with 10 mg/kg of BA. In summary, BA
effectively ameliorates hyperglycemia through inhibition of hepatic
gluconeogenesis via modulating the CAMKK-AMPK-CREB signaling pathway