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

Abstract

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.

Antidiabetic Potential of Monoterpenes: A Case of Small Molecules Punching above Their Weight

“…In this regard, the various effect of monoterpenes in signaling pathways appear to be consistent with antidiabetic effect through upregulation of GLUT4 expression and/or translocation ( Table 1 ). The modulation of the AMPK pathway by natural products that enhance glucose uptake while concomitantly inhibiting gluconeogenesis and stimulation of glycogen synthesis have previously been reported (e.g., [ 128 , 129 , 130 , 131 , 132 ]. Hence, possible multiple mechanisms involving insulin signaling and other pathways involving the AMPK, GLUT4 and PPARγ are at play in the antidiabetic effect of monoterpenes.…”

Dietary Anthocyanins and Insulin Resistance: When Food Becomes a Medicine

“…The AMPK pathway has also been emerged as a major drug target for diabetes and related diseases given its crucial regulatory role in energy metabolism involving glucose and lipids [ 140 ]. The increased phosphorylation of the AMPK pathway by anthocyanin such as those from mulberry fruit extract could not only increase glucose uptake but also inhibit gluconeogenesis and stimulates glycogen synthesis [ 141 ]. The improvement of glucose homeostasis in diabetic mice by cyanidin-3- O -β-glucoside [ 142 ] and dietary anthocyanin-rich bilberry extract [ 67 ] has been shown to be mediated through activation of the AMPK pathway.…”

Protein Tyrosine Phosphatase 1B Inhibition and Glucose Uptake Potentials of Mulberrofuran G, Albanol B, and Kuwanon G from Root Bark of Morus alba L. in Insulin-Resistant HepG2 Cells: An In Vitro and In Silico Study

“…It was also reported that an M. alba leaf extract-containing diet could reduce insulin resistance and may delay the development of diabetes [ 19 ]. Fruit extract from M. alba improved hyperglycemia and insulin sensitivity via activation of the adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and AS160 in skeletal muscles and inhibition of gluconeogenesis in the liver [ 20 ]. Similarly, it was reported that a 70% alcohol extract of M. alba root bark could protect the generation of pancreatic β-cells, and a leaf extract could restore diminished β-cell numbers [ 21 , 22 ].…”