Antihyperglycemic action of syringin
| Autor: | Ho-Shan Niu, 牛河山 |
|---|---|
| Rok vydání: | 2010 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 98 In streptozotocin-induced diabetic rats (STZ-diabetic rats), the type-1 diabetes-like animal model, the mechanism(s) of antihyperglycemic action produced by syringin, an active principle purified from the rhizome part of Eleutherococcus senticosus (Araliaceae),was investigated. Bolus intravenous (i.v.) injection of syringin for 30 min dose-dependently decreased the plasma glucose of STZ-diabetic rats in a way parallel to the increase of plasma ??-endorphin-like immunoreactivity (BER). Syringin enhanced BER release from the isolated adrenal medulla of STZ-diabetic rat in a concentration-dependent manner from 0.001 to 10 ?慆ol/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 ??-opioid receptor antagonists and/or in the ??-opioid receptor knockout diabetic mice. The obtained results suggest that syringin can enhance the secretion of β-endorphin from adrenal medulla to stimulate peripheral ??-opioid receptors resulting in a decrease of plasma glucose in diabetic rats lacking insulin. Syringin at the effective dose (1.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Stimulatory effect of syringin on the glucose uptake was also obtained in the soleus muscles isolated from STZ-diabetic rats in a concentration-dependent manner from 0.01 to 10.0 ?慆ol/l. The increase of glucose utilization by syringin was further characterized using the enhancement of glycogen synthesis in isolated hepatocytes of STZ-diabetic rats. These results suggest that syringin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats lacking insulin. Plasma glucose lowering effect accompanying with the increase of plasma insulin and C-peptide were obtained in pentobarbital anesthetized Wistar rats 60 min after an intravenous (i.v.) injection of syringin (100 μg/kg). However, neither the plasma glucose lowering action, nor the raised plasma levels of insulin and C-peptide can be observed in conscious rats received same syringin treatment. Otherwise, the insulin-releasing and plasma glucose lowering actions of syringin (100 μg/kg, i.v.) were appeared in conscious rats under chemical sympathectomy using an intraperitoneal injection of guanethidine. In addition, plasma glucose lowering action of syringin (100 μg/kg, i.v.) was observed in conscious rats received α1-adrenoceptor blockade with prazosin. The stimulatory actions of syringin on the secretion of plasma insulin and C-peptide were also obtained in prazosin-treated conscious rats. The obtained results suggest that and insulinotropic effect of syringin on the plasma glucose regulation is impaired in conscious rats with a regular sympathetic tone; decrease of sympathetic tone as observed in anesthetized animal is required for actions of syringin. These results suggest that release of β-endorphin from the adrenal gland seems responsible for the lowering of plasma glucose in STZ-diabetic rats by syringin Activation of opioid μ-receptors by the released β-endorphin can increase the utilization of glucose and decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin. However, insulinotropic effect of syringin was interfered with an increase of sympathetic activity in conscious animal; lowering of sympathetic tone might be helpful in the application of syringin. |
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