Document Detail

Effects of troglitazone on substrate storage and utilization in insulin-resistant rats.
MedLine Citation:
PMID:  10362626     Owner:  NLM     Status:  MEDLINE    
Elevated serum and tissue lipid stores are associated with skeletal muscle insulin resistance and diminished glucose-stimulated insulin secretion, the hallmarks of type 2 diabetes. We studied the effects of 6-wk treatment with the insulin sensitizer troglitazone on substrate storage and utilization in lean control and Zucker diabetic fatty (ZDF) rats. Troglitazone prevented development of diabetes and lowered serum triglycerides (TG) in ZDF rats. Soleus muscle glycogen and TG content were elevated twofold in untreated ZDF rats, and both were normalized by troglitazone to lean control levels (P < 0.05). Troglitazone also normalized insulin-stimulated glucose uptake as well as basal and insulin-stimulated glycogen synthesis, implying increased skeletal muscle glycogen turnover. The proportion of active pyruvate dehydrogenase (PDH) in soleus muscle was reduced in ZDF relative to lean control rat muscle (16 +/- 2 vs. 21 +/- 2%) but was restored by troglitazone treatment (30 +/- 3%). Increased PDH activation was associated with a 70% increase in glucose oxidation. Muscle lipoprotein lipase activity was decreased by 35% in ZDF compared with lean control rats and was increased twofold by troglitazone. Palmitate oxidation and incorporation into TG were higher in ZDF relative to lean control rats but were unaffected by troglitazone treatment. Troglitazone decreased the incorporation of glucose into the acyl group of TG by 60% in ZDF rats. In summary, ZDF rats demonstrate increased skeletal muscle glycogen and TG stores, both of which were reduced by troglitazone treatment. Troglitazone appears to increase both glycogen and TG turnover in skeletal muscle. Normalization of PDH activity and decreased glucose incorporation into acyl TG may underlie the improvements in intracellular substrate utilization and energy stores, which lead to decreased serum TG and glucose.
S Sreenan; S Keck; T Fuller; B Cockburn; C F Burant
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  276     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-07-29     Completed Date:  1999-07-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  E1119-29     Citation Subset:  IM    
Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA.
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MeSH Terms
Body Weight / drug effects
Chromans / pharmacology*
Eating / drug effects
Glucose / metabolism
Glycogen / metabolism
Insulin / secretion
Insulin Resistance / genetics,  physiology*
Islets of Langerhans / drug effects,  secretion
Lipoprotein Lipase / metabolism
Muscle, Skeletal / drug effects*,  enzymology,  metabolism*
Palmitates / metabolism
Pyruvate Dehydrogenase Complex / metabolism
Rats, Zucker
Thiazoles / pharmacology*
Triglycerides / blood,  metabolism
Grant Support
Reg. No./Substance:
0/Chromans; 0/Palmitates; 0/Pyruvate Dehydrogenase Complex; 0/Thiazoles; 0/Thiazolidinediones; 0/Triglycerides; 11061-68-0/Insulin; 50-99-7/Glucose; 9005-79-2/Glycogen; 97322-87-7/troglitazone; EC Lipase

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