Mulberry leaf extract displays antidiabetic activity in db/db mice via Akt and AMP-activated protein kinase phosphorylation

Background: Augmenting glucose utilization in skeletal muscle via the phosphatidylinositol-3 kinase (PI3kinase)/protein kinase B (Akt) pathway or the adenosine monophosphate (AMP)-activated protein kinase(AMPK) pathway is necessary to regulate hyperglycemia in patients with type 2 diabetes mellitus. Objective: We investigated the effect of mulberry leaf extract (MLE) on glucose uptake in skeletal muscle cellsand explored its in vivo antidiabetic potential. Design: Male db/db mice were treated with either MLE (50 mg/kg, 100 mg/kg, and 250 mg/kg) or metformin(100 mg/kg) for 8 weeks. Results: MLE treatment stimulated glucose uptake, driven by enhanced translocation of glucose transporter4 to cell membranes in L6 myotubes. These effects of MLE were synergistic with those of insulin and wereabolished in the presence of PI3K inhibitor or AMPK inhibitor. In db/db mice, supplementation with MLEdecreased fasting blood glucose and insulin levels and enhanced insulin sensitivity, with increases of p-Aktand p-AMPK in skeletal muscle. Moreover, MLE improved blood lipid parameters and attenuated hepaticsteatosis in diabetic db/db mice. Discussion: These findings suggest that MLE exerts antidiabetic activity through stimulating glucose disposalin skeletal muscle cells via the PI3K/Akt and AMPK pathways. Conclusions: MLE can potentially improve hyperglycemia and hepatic steatosis in patients with type 2 diabetes.