Mulberry (Morus alba L.) Fruit Extract Containing Anthocyanins Improves Glycemic Control and Insulin Sensitivity via Activation of AMP-Activated Protein Kinase in Diabetic C57BL/Ksj-db/db Mice

The effect of mulberry (Morus alba L.) fruit extract (MFE) on hyperglycemia and insulin sensitivity in an animal model of type 2 diabetes was evaluated. C57BL/Ksj-diabetic db/db mice were divided into three groups: diabetic control, rosiglitazone, and MFE groups. Blood glucose, plasma insulin, and intraperitoneal glucose were measured, and an insulin tolerance test was performed after MFE supplementation in db/db mice. In addition, the protein levels of various targets of insulin signaling were measured by western blotting. The blood levels of glucose and HbA1c were significantly lower in the MFE-supplemented group than in the diabetic control group. Moreover, glucose and insulin tolerance tests showed that MFE treatment increased insulin sensitivity. The homeostatic index of insulin resistance significantly decreased in the MFE-supplemented group relative to the diabetic control group. MFE supplementation significantly stimulated the levels of phosphorylated (p)-AMP-activated protein kinase (pAMPK) and p-Akt substrate of 160 kDa (pAS160) and enhanced the level of plasma membrane-glucose transporter 4 (GLUT4) in skeletal muscles. Further, dietary MFE significantly increased pAMPK and decreased the levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. MFE may improve hyperglycemia and insulin sensitivity via activation of AMPK and AS160 in skeletal muscles and inhibition of gluconeogenesis in the liver.