1 research outputs found
Pentacyclic Triterpenoids from Astilbe rivularis that Enhance Glucose Uptake via the Activation of Akt and Erk1/2 in C2C12 Myotubes
Glucose uptake into insulin-sensitive
tissues is important for the regulation of blood glucose. This study
has investigated whether the pentacyclic triterpenoids substituted
with a carboxylic acid at the C-27 position isolated from Astilbe rivularis can enhance glucose uptake and
subsequently to also examine their underlying molecular mechanisms.
The structure of the new pentacyclic triterpenoid <b>1</b> was
assigned by spectroscopic data interpretation. To evaluate the activity
of compounds <b>1</b> and <b>2</b>, glucose uptake and
glucose transporter 4 (GLUT4) translocation were measured in C2C12
myotubes. The C-27-carboxylated triterpenoids <b>1</b> and <b>2</b> significantly increased basal and insulin-stimulated glucose
uptake and GLUT4 translocation to plasma membrane. Both compounds
stimulated the phosphorylation of insulin receptor substrate-1 (IRS-1),
protein kinase B (Akt), and extracellular signal-regulated kinase
1/2 (Erk1/2). Pretreatment with the Akt inhibitor triciribine or the
Erk1/2 inhibitor U0126 decreased the ability of both compounds to
enhance basal- and insulin-stimulated glucose uptake and stimulate
GLUT4 translocation. These results indicate that compounds <b>1</b> and <b>2</b> activated both the IRS-1/Akt and Erk1/2 pathways
and subsequently stimulated GLUT4 translocation, leading to enhanced
glucose uptake. Thus, these observations suggest that C-27-carboxylated-pentacyclic
triterpenoids may serve as scaffolds for development as agents for
the management of blood glucose levels in disease states such as diabetes