Document Detail


Topiramate treatment causes skeletal muscle insulin sensitization and increased Acrp30 secretion in high-fat-fed male Wistar rats.
MedLine Citation:
PMID:  16030065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We show that Topiramate (TPM) treatment normalizes whole body insulin sensitivity in high-fat diet (HFD)-fed male Wistar rats. Thus drug treatment markedly lowered glucose and insulin levels during glucose tolerance tests and caused increased insulin sensitization in adipose and muscle tissues as assessed by euglycemic clamp studies. The insulin-stimulated glucose disposal rate increased twofold (indicating enhanced muscle insulin sensitivity), and suppression of circulating FFAs increased by 200 to 300%, consistent with increased adipose tissue insulin sensitivity. There were no effects of TPM on hepatic insulin sensitivity in these TPM-treated HFD-fed rats. In addition, TPM administration resulted in a three- to fourfold increase in circulating levels of total and high-molecular-weight (HMW) adiponectin (Acrp30). Western blot analysis revealed normal AMPK (Thr(172)) phosphorylation in liver with a twofold increased phospho-AMPK in skeletal muscle in TPM-treated rats. In conclusion, 1) TPM treatment prevents overall insulin resistance in HFD male Wistar rats; 2) drug treatment improved insulin sensitivity in skeletal muscle and adipose tissue associated with enhanced AMPK phosphorylation; and 3) the tissue "specific" effects are associated with increased serum levels of adiponectin, particularly the HMW component.
Authors:
Jason J Wilkes; M T Audrey Nguyen; Gautam K Bandyopadhyay; Elizabeth Nelson; Jerrold M Olefsky
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2005-07-19
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  289     ISSN:  0193-1849     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-11-10     Completed Date:  2005-12-21     Revised Date:  2013-08-21    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1015-22     Citation Subset:  IM    
Affiliation:
Division of Endocrinology and Metabolism, Department of Medicine, University of California-San Diego, 0673 UCSD, 9500 Gilman Drive, La Jolla, CA 92093, USA. jwilkes@gnf.org
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases
Adiponectin / blood,  secretion
Adipose Tissue / drug effects
Animals
Anti-Obesity Agents / administration & dosage*
Blood Glucose / analysis
Dietary Fats / administration & dosage*
Fatty Acids, Nonesterified / blood
Fructose / administration & dosage,  analogs & derivatives*
Glucose Clamp Technique
Insulin / blood,  pharmacology*
Insulin Resistance
Liver / enzymology
Male
Multienzyme Complexes / metabolism
Muscle, Skeletal / drug effects*,  physiology
Phosphorylation
Protein-Serine-Threonine Kinases / metabolism
Rats
Rats, Wistar
Grant Support
ID/Acronym/Agency:
DK 33651/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Adiponectin; 0/Adipoq protein, rat; 0/Anti-Obesity Agents; 0/Blood Glucose; 0/Dietary Fats; 0/Fatty Acids, Nonesterified; 0/Insulin; 0/Multienzyme Complexes; 0H73WJJ391/topiramate; 30237-26-4/Fructose; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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