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
Original Article

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.

Keywords

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

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Bu Chin Yu
    • 1
  • Cheng Kuei Chang
    • 2
  • Chih Fen Su
    • 3
  • Juei Tang Cheng
    • 1
  1. 1.Institute of Basic Medical Science, and Department of Pharmacology, College of MedicineNational Cheng Kung UniversityTainan CityRepublic of China
  2. 2.Department of Surgery, Mackay Memorial Hospital, and Graduate Institute of Injury Prevention and ControlTaipei Medical UniversityTaipei CityRepublic of China
  3. 3.Department of NursingNational Tainan Institute of NursingTainan CityRepublic of China

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