Document Detail


Pachymic acid stimulates glucose uptake through enhanced GLUT4 expression and translocation.
MedLine Citation:
PMID:  20816811     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In an effort to investigate the effect and mechanism of Poria cocos on glucose uptake, six lanostane-type triterpenoids were isolated and analyzed. Among them, pachymic acid displayed the most significant stimulating activity on glucose uptake in 3T3-L1 adipocytes. The effect of pachymic acid on the expression profile of glucose transporters in differentiated 3T3-L1 adipocytes was also analyzed. Our results demonstrated that pachymic acid induced an increase in GLUT4, but not GLUT1, expression at both the mRNA and protein levels. The role of GLUT4 was further confirmed using the lentiviral vector-derived GLUT4 short hairpin RNA (shRNA). The stimulating activity of pachymic acid on glucose uptake was abolished when the endogenous GLUT4 expression was suppressed in 3T3-L1 adipocytes. In addition to increased GLUT4 expression, pachymic acid stimulated GLUT4 redistribution from intracellular vesicles to the plasma membrane in adipocytes. Exposure of the differentiated adipocytes to pachymic acid increased the phosphorylation of insulin receptor substrate (IRS)-1, AKT and AMP-activated kinase (AMPK). The involvement of PI3K and AMPK in the action of pachymic acid was further confirmed as PI3K and AMPK inhibitors completely blocked the pachymic acid-mediated activities in adipocytes. In addition, pachymic acid was shown to induce triglyceride accumulation and inhibit lipolysis in differentiated adipocytes. Taken together, we demonstrated the insulin-like activities of this compound in stimulating glucose uptake, GLUT4 gene expression and translocation, and promoting triglyceride accumulation in adipocytes. Our study provides important insights into the underlying mechanism of hypoglycemic activity of P. cocos.
Authors:
Yu-Chuan Huang; Wen-Liang Chang; Su-Fen Huang; Cheng-Yu Lin; Hang-Ching Lin; Tsu-Chung Chang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-09
Journal Detail:
Title:  European journal of pharmacology     Volume:  648     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-12     Completed Date:  2011-01-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  39-49     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan, ROC. alexha@mail.ndmctsgh.edu.tw
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MeSH Terms
Descriptor/Qualifier:
3T3-L1 Cells
Adenylate Kinase / metabolism
Adipocytes / cytology,  drug effects,  metabolism
Animals
Cell Differentiation / drug effects
Gene Expression Regulation / drug effects*
Glucose / metabolism*
Glucose Transporter Type 4 / genetics*,  metabolism*
Hypoglycemic Agents / isolation & purification,  pharmacology*
Lipolysis / drug effects
Mice
Phosphatidylinositol 3-Kinases / metabolism
Poria / chemistry
Protein Transport / drug effects
RNA, Messenger / genetics,  metabolism
Signal Transduction / drug effects
Triglycerides / metabolism
Triterpenes / isolation & purification,  pharmacology*
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 4; 0/Hypoglycemic Agents; 0/RNA, Messenger; 0/Triglycerides; 0/Triterpenes; 29070-92-6/pachymic acid; 50-99-7/Glucose; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.4.3/Adenylate Kinase

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