Cyanidin-3-O-β-glucoside and protocatechuic acid activate AMPK/mTOR/S6K pathway and improve glucose homeostasis in mice

• C3G and PCA activate AMPK and inhibit mTOR and S6K.
• C3G and PCA upregulate glucose transporters.
• C3G and PCA improve glucose tolerance and insulin sensitivity.
• PCA sources are promising protectors for type-2 diabetes.
• Blood orange juice improves insulin sensitivity.

AMP-activated protein kinase (AMPK) activation is an established treatment for diabetes. Here the effects of anthocyanin extract from blood orange juice, i.e. cyanidin-3-O-β-glucoside (C3G) and its secondary metabolite protocatechuic acid (PCA), on AMPK signalling in murine hepatic cell line and in the liver of C57BL/6 mice were investigated. Results showed for the first time that C3G and PCA activate AMPK and suppress its downstream kinase mTOR/S6K both in vitro and in vivo systems. Then, C3G and particularly PCA increased expression of glut 1 and glut 4 in the liver and improved glucose tolerance in normal and obese mice. Finally, the consumption of blood orange juice was observed to increase insulin sensitivity in mice. These findings indicate that C3G and PCA are natural AMPK activators and dietary consumption of food sources of C3G and PCA improves glucose homeostasis. Mainly, blood orange juice has beneficial effect for type 2 diabetes.