It is well known that
propolis has the ability to prevent
hyperglycemia. However, the underlying mechanism is not yet fully understood. We therefore investigated whether a Brazilian
propolis ethanol extract affects
glucose uptake and translocation of
insulin-sensitive
glucose transporter (GLUT) 4 in skeletal muscle cells. In L6 myotubes, the extract at 1 μg/mL significantly promoted GLUT4 translocation and
glucose uptake activity. Regarding the mechanism of GLUT4 translocation,
propolis extract induced both PI3K and AMPK phosphorylation in a dose-dependent manner in L6 myotubes. However, we could not define which pathway was preferentially associated with GLUT4 translocation, because both PI3K and AMPK inhibitors revealed off-target effects to each other. The main
polyphenols found in the
propolis extract,
artepillin C,
coumaric acid, and
kaempferide, promoted GLUT4 translocation in L6 myotubes. Additionally, these compounds activated both PI3K- and AMPK-dependent dual-signaling pathways. However, only
kaempferide increased
glucose uptake activity under our experimental conditions. Single
oral administrations of
propolis extract, at 250 mg/kg
body weight, lowered postprandial
blood glucose levels in ICR mice. The extract promoted GLUT4 translocation in skeletal muscle of rats and mice, but did not inhibit α-
glucosidase activity in the small intestine under our experimental conditions. It was confirmed that
propolis extract promoted phosphorylation of both PI3K and AMPK in rat skeletal muscle. In conclusion, we show that Brazilian
propolis has the potential to prevent
hyperglycemia through the promotion of GLUT4 translocation in skeletal muscle and that
kaempferide is one of the candidates for active compound in
propolis.