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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-6
pubmed:dateCreated
2008-6-19
pubmed:abstractText
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 beta-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-alpha-dimethyl-1H-indole-3-thylamine (RS17053) at doses sufficient to block alpha1-adrenoceptors (ARs). Also, andrographolide enhanced BER release from isolated rat adrenal medulla in a concentration-related manner that could be abolished by alpha1-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 micro-receptor antagonists and in the opioid micro-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 micro-receptor antagonists. In conclusion, our results suggest that andrographolide may activate alpha1-ARs to enhance the secretion of beta-endorphin which can stimulate the opioid micro-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 micro-receptors associated with the plasma glucose-lowering action of andrographolide, should be considered and need more investigation in the future.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
377
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
529-40
pubmed:meshHeading
pubmed-meshheading:18080810-Animals, pubmed-meshheading:18080810-Blood Glucose, pubmed-meshheading:18080810-Diabetes Mellitus, Experimental, pubmed-meshheading:18080810-Diabetes Mellitus, Type 1, pubmed-meshheading:18080810-Diterpenes, pubmed-meshheading:18080810-Dose-Response Relationship, Drug, pubmed-meshheading:18080810-Gene Expression Regulation, pubmed-meshheading:18080810-Glucose Transporter Type 4, pubmed-meshheading:18080810-Hypoglycemic Agents, pubmed-meshheading:18080810-Liver, pubmed-meshheading:18080810-Male, pubmed-meshheading:18080810-Mice, pubmed-meshheading:18080810-Mice, Knockout, pubmed-meshheading:18080810-Muscle, Skeletal, pubmed-meshheading:18080810-Rats, pubmed-meshheading:18080810-Rats, Wistar, pubmed-meshheading:18080810-Receptors, Opioid, mu, pubmed-meshheading:18080810-Streptozocin, pubmed-meshheading:18080810-beta-Endorphin
pubmed:year
2008
pubmed:articleTitle
Mediation of beta-endorphin in andrographolide-induced plasma glucose-lowering action in type I diabetes-like animals.
pubmed:affiliation
Institute of Basic Medical Science, and Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan, 70101, Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't