Mulberry (Morus alba L.) Leaf Extract and 1-Deoxynojirimycin Improve Skeletal Muscle Insulin Resistance via the Activation of IRS-1/PI3K/Akt Pathway in db/db Mice

Mulberry (Morus alba L.) leaves have been used to lower blood glucose in patients with diabetes. We evaluated the effects of mulberry leaves extract (MLE) and 1-deoxynojirimycin (1-DNJ) in improving insulin resistance through the activation of the IRS-1/PI3K/Akt pathway in the skeletal muscle of db/db mice. Histological analysis revealed an amelioration of muscle deformation and increased muscle fiber size. MLE and 1-DNJ positively raised the protein expression of related glucose uptake and increased the translocation of glucose transporter type 4 (GLUT4) to the membrane. Furthermore, MLE and 1-DNJ activated the IRS-1/PI3K/Akt pathway in the skeletal muscle and, subsequently, modulated the protein levels of glycogen synthase kinase-3beta (GSK-3β) and glycogen synthase (GS), leading to elevated muscle glycogen content. These findings suggest that MLE and 1-DNJ supplementation improves insulin resistance by modulating the insulin signaling pathway in the skeletal muscle of db/db mice.