Puerarin acts on the skeletal muscle to improve insulin sensitivity in diabetic rats involving μ-opioid receptor

Puerarin, a major active isoflavone extracted from the root of Pueraria lobate, significantly increases plasma beta-endorphin and insulin levels and improves impaired insulin signaling in diabetic animals. However, the target tissues and underlying mechanisms in and through which puerarin functions to ameliorating insulin resistance remains largely unclear. In this study, we showed that puerarin enhanced mu-opioid receptor expression and phosphorylation, and increased insulin-stimulated glucose transporter 4 translocation to the plasma membrane in the skeletal muscle of diabetic rats, which were recaptured by a direct application of puerarin in the palmitate-induced insulin-resistant L6 myotubes. Naloxone, an antagonist of mu-opioid receptor, blocked these functions of puerarin. No beta-endorphin was detected either in the muscle of diabetic rats or in the palmitate-induced insulin-resistant L6 cells. Furthermore, we presented the evidence to show the interaction between mu-opioid receptor and insulin receptor substrate 1 in the muscle tissues and cells. These results suggested that puerarin improved insulin sensitivity in the skeletal muscle at least in part by its local effects involving mu-opioid receptor function.