Piperine Promotes Glucose Uptake through ROS-Dependent Activation of the CAMKK/AMPK Signaling Pathway in Skeletal Muscle.

SCOPE: The prevalence of type 2 diabetes mellitus (T2DM) is increasing yearly worldwide. Glycemic control is the basis for the treatment of T2DM, as it can prevent the progress of associated complications. Spices possess various health beneficial effects on humans. The aim of this study is to search for spices that can promote glucose uptake and to elucidate the underlying molecular mechanism(s). METHODS AND RESULTS: Among 24 spice extracts, the extracts from black pepper and white pepper significantly increase glucose uptake in L6 myotubes. Piperine is found to be the active compound in these extracts. Treatment of myotubes with piperine induces the translocation of glucose transporter 4 (GLUT4) to the plasma membrane by phosphorylation of AMP-activated protein kinase (AMPK). Piperine increases the intracellular Ca2+ level and reactive oxygen species (ROS) generation through transient receptor potential vanilloid channel 1 (TRPV1), followed by activation of Ca2+ /calmodulin-dependent protein kinase kinase-beta (CaMKKß) as the upstream events for AMPK phosphorylation. Furthermore, oral administration of piperine to Wistar rats at 0.01 and 0.1 mg kg-1 body weight decreases postprandial hyperglycemia accompanied by GLUT4 translocation and AMPK phosphorylation. CONCLUSION: Piperine in pepper prevents hyperglycemia by GLUT4 translocation through CaMKKß/AMPK signaling via TRPV1-dependent increase in the intracellular Ca2+ level and ROS generation.

Screening plant derived dietary phenolic compounds for bioactivity related to cardiovascular disease.

The potential health benefits of phenolic acids found in food and beverages has been suggested from a number of large population studies. However, the mechanism of how these compounds may exert biological effects is less well established. It is also now recognised that many complex polyphenols in the diet are metabolised to simple phenolic acids which can be taken up in the circulation. In this paper a number of selected phenolic compounds have been tested for their bioactivity in two cell culture models. The expression and activity of endothelial nitric oxide synthase (eNOS) in human aortic endothelial cells and the uptake of glucose in muscle cells. Our data indicate that while none of the compounds tested had a significant effect on eNOS expression or activation in endothelial cells, several of the compounds increased glucose uptake in muscle cells. These compounds also enhanced the translocation of the glucose transporter GLUT4 to the plasma membrane, which may explain the observed increase in cellular glucose uptake. These results indicate that simple cell culture models may be useful to help understand the bioactivity of phenolic compounds in relation to cardiovascular protection.