Document Detail


Insulin-independent and extremely rapid switch in the partitioning of hepatic fatty acids from oxidation to esterification in starved-refed diabetic rats. Possible roles for changes in cell pH and volume.
MedLine Citation:
PMID:  7848296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The requirement for a normal insulin response in mediating the starved-to-refed transition, with respect to the partitioning of hepatic fatty acids between beta-oxidation and esterification to glycerol, was studied. Diabetic rats were starved for 24 h and refed ad libitum for various periods of time. There was no increase in plasma insulin in response to the meal. However, the fatty acid oxidation:esterification ratio was very rapidly decreased from the starved to the fed value, most of the transition being achieved within the first hour of refeeding. There was a 2 h lag in the response of hepatic malonyl-CoA concentration, such that this rapid switch from oxidation to esterification could not be explained on the basis of changes in the absolute concentration of this inhibitor of carnitine palmitoyltransferase I (CPT I). Hepatic pyruvate and lactate concentrations both increased by several-fold upon refeeding and peaked after 1 h and 3 h, respectively. The hepatic lactate:pyruvate ratio increased 3.2-fold during the first 3 h of refeeding, suggesting that the cytosolic NAD(+)-NADH couple became much more highly reduced during the lag-period between the onset of inhibition of flux of fatty acids towards oxidation and the rise in malonyl-CoA concentration. This may be indicative of a lowering of intracellular pH, which would amplify greatly the sensitivity of CPT I to the inhibitor. In view of the very rapid and high food intake by these diabetic rats, the possibility is also considered that portal concentrations of amino acids and other metabolites could give rise to an increase in liver cell-volume that would inhibit CPT I acutely by an as yet unknown mechanism [M. Guzman, G. Velasco, J. Castro and V. A. Zammit (1994) FEBS Lett. 344, 239-241].
Authors:
A M Moir; V A Zammit
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  305 ( Pt 3)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1995 Feb 
Date Detail:
Created Date:  1995-03-08     Completed Date:  1995-03-08     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  953-8     Citation Subset:  IM    
Affiliation:
Hannah Research Institute, Ayr, U.K.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carnitine O-Palmitoyltransferase / metabolism
Cholesterol Esters / metabolism
Diabetes Mellitus, Experimental / metabolism*
Esterification
Fatty Acids / metabolism*
Fatty Acids, Nonesterified / blood
Female
Food
Glycerophosphates / metabolism
Insulin / blood,  pharmacology*
Lactates / blood,  metabolism
Lactic Acid
Liver / metabolism*
Malonyl Coenzyme A / metabolism,  pharmacology
Mitochondria, Liver / drug effects,  enzymology
Oxidation-Reduction
Pyruvates / blood,  metabolism
Pyruvic Acid
Rats
Rats, Wistar
Starvation / metabolism*
Chemical
Reg. No./Substance:
0/Cholesterol Esters; 0/Fatty Acids; 0/Fatty Acids, Nonesterified; 0/Glycerophosphates; 0/Lactates; 0/Pyruvates; 11061-68-0/Insulin; 127-17-3/Pyruvic Acid; 303-43-5/cholesteryl oleate; 50-21-5/Lactic Acid; 524-14-1/Malonyl Coenzyme A; 57-03-4/alpha-glycerophosphoric acid; EC 2.3.1.21/Carnitine O-Palmitoyltransferase
Comments/Corrections

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