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 journalArticle

39 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

Fingerprint

Endorphins
Type 1 Diabetes Mellitus
Glucose
Streptozocin
Opioid Receptors
Adrenergic Receptors
Opioid Peptides
Narcotic Antagonists
Skeletal Muscle
andrographolide
Phosphoenolpyruvate
Adrenal Medulla
Gluconeogenesis
Facilitative Glucose Transport Proteins
Prazosin
Liver
Adrenalectomy
Knockout Mice

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Mediation of β-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals. / Yu, Bu Chin; Chang, Cheng Kuei; Su, Chih Fen; Cheng, Juei Tang.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 377, No. 4-6, 06.2008, p. 529-540.

Research output: Contribution to journalArticle

@article{fb21b1cdf546430f8dc74183cb25b5a3,
title = "Mediation of β-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals",
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 = "β-Endorphin, Andrographolide, Opioid μ-receptor, STZ-diabetic rats",
author = "Yu, {Bu Chin} and Chang, {Cheng Kuei} and Su, {Chih Fen} and Cheng, {Juei Tang}",
year = "2008",
month = "6",
doi = "10.1007/s00210-007-0240-0",
language = "English",
volume = "377",
pages = "529--540",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "4-6",

}

TY - JOUR

T1 - Mediation of β-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals

AU - Yu, Bu Chin

AU - Chang, Cheng Kuei

AU - Su, Chih Fen

AU - Cheng, Juei Tang

PY - 2008/6

Y1 - 2008/6

N2 - 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.

AB - 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.

KW - β-Endorphin

KW - Andrographolide

KW - Opioid μ-receptor

KW - STZ-diabetic rats

UR - http://www.scopus.com/inward/record.url?scp=45849092979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45849092979&partnerID=8YFLogxK

U2 - 10.1007/s00210-007-0240-0

DO - 10.1007/s00210-007-0240-0

M3 - Article

VL - 377

SP - 529

EP - 540

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 4-6

ER -