Document Detail

Exercise in transgenic mice overexpressing GLUT4 glucose transporters: effects on substrate metabolism and glycogen regulation.
MedLine Citation:
PMID:  9361698     Owner:  NLM     Status:  MEDLINE    
We assessed the effects of GLUT4 glucose transporter expression on substrate metabolism and glycogen regulation during exercise. Transgenic mice overexpressing human (h)GLUT4 in muscle and fat (TG) and their wild-type littermates (WT) were studied by indirect calorimetry at rest and during acute treadmill exercise (30 minutes) and recovery (30 minutes). The rate of carbon dioxide production (VCO2) increased to a greater degree in TG during exercise, whereas resting VCO2, resting oxygen production (VO2), and exercise-induced increments in VO2 were similar in TG and WT. As a result, the respiratory quotient (RQ) was increased by .03 to .05 in TG during exercise, due to greater consumption of carbohydrate (up to approximately 64% more) and less consumption of lipid (up to approximately 40% less) compared with WT, without differences in overall energy expenditure. These differences in substrate metabolism were observed despite relative hypoglycemia and elevated free fatty acids (FFAs) in TG that persisted throughout resting, exercise, and recovery periods. To further assess substrate availability, glycogen content and glycogen synthase activity were measured in skeletal muscle and liver. At rest, muscle glycogen content was 50% higher and glycogen synthase I was 40% lower in TG compared with WT. During exercise and recovery, muscle glycogen was more profoundly depleted in TG than in WT, and glycogen synthase I increased to levels observed in WT, with no change in total glycogen synthase. In the liver, glycogen content and total glycogen synthase were similar in TG and WT under resting conditions, while glycogen synthase I was reduced by 48%. Exercise and recovery induced a more profound depletion of liver glycogen (76% v 30%) and greater increments in both I-form and total glycogen synthase in TG. In conclusion, (1) TG overexpressing GLUT4 exhibit greater muscle glycogen content at rest than WT; (2) during exercise, TG metabolize more carbohydrate, made possible by increased glycogenolysis in muscle and liver, and this predominates as a fuel source despite hypoglycemia and increased availability of FFA; (3) increased carbohydrate metabolism is linked to a decrease in lipid metabolism such that there is no change in overall energy expenditure; and (4) glycogen synthase I activity is inversely proportional to tissue glycogen content despite differences in circulating glucose, insulin, and FFA concentrations, indicating that glycogen content has an overriding regulatory influence on glycogen synthase.
S Bao; W T Garvey
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  46     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-02     Completed Date:  1997-12-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1349-57     Citation Subset:  IM; S    
Department of Medicine, Medical University of South Carolina, Charleston, USA.
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MeSH Terms
Basal Metabolism
Blood Glucose / analysis,  genetics,  metabolism
Body Weight
Energy Metabolism / genetics,  physiology*
Fatty Acids, Nonesterified / blood,  genetics,  metabolism
Gene Expression Regulation, Developmental / genetics
Genetic Engineering
Glucose Transporter Type 4
Glycogen / analysis,  genetics,  metabolism*
Glycogen Synthase / genetics,  metabolism
Liver / chemistry,  enzymology,  metabolism*
Mice, Inbred C57BL
Mice, Transgenic
Monosaccharide Transport Proteins / analysis,  biosynthesis,  genetics*
Muscle Proteins*
Muscles / chemistry,  enzymology,  metabolism*
Oxygen Consumption / genetics,  physiology*
Physical Conditioning, Animal / physiology*
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids, Nonesterified; 0/Glucose Transporter Type 4; 0/Monosaccharide Transport Proteins; 0/Muscle Proteins; 0/SLC2A4 protein, human; 0/Slc2a4 protein, mouse; 9005-79-2/Glycogen; EC Synthase

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