We employed streptozotocin-induced diabetic rats (STZ-diabetic rats) as type 1 diabetes-like animal models to investigate the mechanism(s) of antihyperglycemic action produced by syringin, an active principle purified from the rhizome and root parts of Eleutherococcus senticosus (Araliaceae). Bolus intravenous (i.v.) injection of syringin dose-dependently decreased the plasma glucose of STZ-diabetic rats in 30 minutes in a way parallel to the increase of plasma β-endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the isolated adrenal medulla of STZ-diabetic rats in a concentration-dependent manner from 0.001 to 10 μmol/l. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of syringin (1 mg/kg, i.v.) including the plasma glucose-lowering effect and the plasma BER-elevating effect. Also, syringin failed to lower plasma glucose in the presence of μ-opioid receptor antagonists and/or in the μ-opioid receptor knockout diabetic mice. In conclusion, the obtained results suggest that syringin can enhance the secretion of β-endorphin from adrenal medulla to stimulate peripheral μ-opioid receptors resulting in a decrease of plasma glucose in diabetic rats lacking insulin.
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