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.