Abstract
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.
Highlights
Diabetes is a metabolic disorder characterized by hyperglycemia and caused by increased hepatic glucose production, abnormal glucose utilization in peripheral tissues, and inadequate insulin secretion [1]
Type 2 insulin-resistant diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycemia and dyslipidemia resulting from peripheral tissue insulin resistance and impaired insulin secretion from the pancreas [13]
Intensive treatment to control hyperglycemia is needed in diabetes
Summary
Diabetes is a metabolic disorder characterized by hyperglycemia and caused by increased hepatic glucose production, abnormal glucose utilization in peripheral tissues, and inadequate insulin secretion [1]. Several approaches have been recommended to reduce hyperglycemia, including increasing pancreatic insulin release by sulfonylureas, decreasing hepatic glucose production by metformin, enhancing insulin action by thiazolidinediones, and suppressing gut glucose absorption by α-glucosidase. These treatments have limited efficacy, a high likelihood of tolerability issues, and significant mechanismbased side effects [1]. & Maxim.) is called Harms (ES), Acanthopanax senticosus, Siberian ginseng, or Gasiogapi in Korea It is a well-known tonic and sedative Chinese herb that affects various diseases with its antibacterial, antifatigue [3], antioxidant [4], and immunomodulating [5] activities. The insulin signaling pathway in skeletal muscle and mRNA expression of hepatic metabolism-related genes were evaluated to determine the molecular mechanisms of ES and EE-induced activity
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