The mechanism study underlying glucose uptake mediated by Canarium album in 3T3-L1 Adipocytes

Diabetes ranks the fourth leading cause of death in Taiwan, according to the latest report by Ministry of Health and Welfare, and the prevalence is going up. The major cause of diabetes is obesity-induced insulin resistance, which is reduced glucose uptake by peripheral tissues due to compromised sensitivity to insulin as a result of excess lipid accumulation in adipose tissues. Chinese olive is rich in bioactive compounds such as phenolics and flavonoids, and shows anti-inflammatory, antibacterial, anti-oxidative, and anti-proliferative effects. Previous in vivo studies indicate that the ethyl acetate fraction of methanol extract of Chinese olive (COE) ameliorates diabetes. The present study then aims to investigate the underlying mechanism for COE’s anti-diabetic effects using 3T3-L1 mouse adipocytes. Results of glucose uptake test show COE stimulates the uptake of 2-NBDG by mature adipocytes, and such effect is not ablated in the presence of insulin resistance, nor completely abolished by the use of inhibitors for PI3K, GLUT, or AMPK. In addition, treatment of COE can dose-dependently increase transcription of the glucose transporter 1 gene in 3T3-L1. Its regulatory role in AMPK activity in 3T3-L1 is not certain, but it is clear that COE can stimulate the expression of AKT and increase GLUT4 translocation to plasma membrane. Therefore it is postulated that the mechanism behind COE’s stimulatory effect on glucose uptake of adipocytes is different from PI3K and AMPK signaling pathways. Further study is needed to understand the underlying mechanism of how COE increases GLUT1 gene expression and glucose uptake.