Mediation of β-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals

Bu Chin Yu, Cheng Kuei Chang, Chih Fen Su, Juei Tang Cheng

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

In the present study, we investigated the mechanism(s) for glucose-lowering action of andrographolide in streptozotocin-induced diabetic rats (STZ-diabetic rats). Andrographolide lowered plasma glucose concentrations in a dose-dependent manner and increased plasma β-endorphin-like immunoreactivity (BER) dose-dependently in diabetic rats. Both of these responses to andrographolide were abolished by the pretreatment of animals with prazosin or N-(2 -(2-cyclopropylmethoxy) ethyl) 5-choro-α-dimethyl-1H- indole-3-thylamine (RS17053) at doses sufficient to block α1- adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by α1-ARs antagonists. Bilateral adrenalectomy in STZ-diabetic rats eliminated the activities of andrographolide, including the plasma glucose-lowering effect and the plasma BER-elevating effect. Andrographolide failed to lower plasma glucose in the presence of opioid μ-receptor antagonists and in the opioid μ-receptor knockout diabetic mice. Treatment of STZ-diabetic rats with andrographolide resulted in the reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver and an increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle. These effects were also blocked by opioid μ-receptor antagonists. In conclusion, our results suggest that andrographolide may activate α1-ARs to enhance the secretion of β-endorphin which can stimulate the opioid μ-receptors to reduce hepatic gluconeogenesis and to enhance the glucose uptake in soleus muscle, resulting in a decrease of plasma glucose in STZ-diabetic rats. However, the roles of other endogenous opioid peptides or the mixture of several opioid peptides in the activation of opioid μ-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.

Original languageEnglish
Pages (from-to)529-540
Number of pages12
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume377
Issue number4-6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • β-Endorphin
  • Andrographolide
  • Opioid μ-receptor
  • STZ-diabetic rats

ASJC Scopus subject areas

  • Pharmacology

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