Defective regulation of energy metabolism in mdx-mouse skeletal muscles.
Our previous finding of a reduced energy metabolism in slow- and fast-twitch skeletal muscle fibres from the murine model of Duchenne muscular dystrophy (the mdx mouse) led us to examine the importance of intracellular glucose availability for a normal energy turnover. To this end, basal and KCl-stimulated (20.9 mM total extracellular K+) rates of glucose uptake (GUP) and heat production were measured in isolated, glucose-incubated (5 mM) soleus and extensor digitorum longus muscles from mdx and control C57B1/10 mice, in the presence and in the absence of insulin (1.7 nM). Under all conditions and for both muscle types, glucose uptake values for mdx and control muscles were similar although heat production was lower in mdx muscles. The marked stimulation of GUP by insulin in both mdx and control muscles had only minor effects on heat production. In contrast, glucose deprivation or inhibition of glycolysis with 2-deoxy-D-glucose (5 mM) significantly decreased heat production in control muscles only, which attenuated, although did not suppress, the difference in basal heat production between mdx and control muscles. Stimulation of heat production by a short-chain fatty acid salt (octanoate, 2 mM) was significantly less marked in mdx than in control muscles. Increased cytoplasmic synthesis of CoA by addition of 5 mM pantothenate (vitamin B5) increased the thermogenic response to glucose more in mdx than in control muscles. We conclude that the low energy turnover in mdx-mouse muscle fibres is not due to a decrease of intracellular glucose availability, but rather to a decreased oxidative utilization of glucose and free fatty acids. We suggest that some enzyme complex of the tricarboxylic acid cycle or inefficiency of CoA transport in the mitochondria could be involved.
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Laboratoire de Neurobiologie des Régulations, C.N.R.S. UA 637, Collège de France, Paris.
Decrouy
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Chinet
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D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002210:Caprylates / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010205:Pantothenic Acid / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology
D002210:Caprylates; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010205:Pantothenic Acid; D011189:Potassium Chloride; D003847:Deoxyglucose; D005947:Glucose; C031492:octanoic acid; D002118:Calcium