Eleutheroside E, An Active Component of Eleutherococcus senticosus, Ameliorates Insulin Resistance in Type 2 Diabetic db/db Mice

Eleutheroside E (EE), a principal component of Eleutherococcus senticosus (ES), has anti-inflammatory and protective effects in ischemia heart. However, it is unknown whether it ameliorates insulin resistance and reduces hyperglycemia in diabetes. This study investigated the effect of EE-containing ES extracts, as well as EE, on hyperglycemia and insulin resistance in db/db mice. EE increased the insulin-provoked glucose uptake in C2C12 myotubes. Moreover, EE improved TNF-α-induced suppression of glucose uptake in 3T3-L1 adipocytes. Five-week-old db/db mice were fed a diet consisting of ES extract or EE for 5 weeks. Both were effective in improving serum lipid profiles and significantly decreased blood glucose and serum insulin levels. ES and EE supplementation effectively attenuated HOMA-IR. Glucose tolerance and insulin tolerance tests showed that EE increased insulin sensitivity. Immunohistochemical staining indicated that ES and EE protected pancreatic alpha and beta cells from diabetic damage. In addition, ES and EE improved hepatic glucose metabolism by upregulating glycolysis and downregulating gluconeogenesis in obese type 2 diabetic mice. These data suggest that EE mediates the hyperglycemic effects of ES by regulating insulin signaling and glucose utilization. The beneficial effects of EE may provide an effective and powerful strategy to alleviate diabetes.