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 muscul ar dystrophy (the mdx mouse) led us to examine the importance of intra cellular glucose availability for a normal energy turnover. To this en d, basal and KCl-stimulated (20.9 mM total extracellular K+) rates of glucose uptake (GUP) and heat production were measured in isolated, gl ucose-incubated (5 mM) soleus and extensor digitorum longus muscles fr om mdx and control C57B1/10 mice, in the presence and in the absence o f insulin (1.7 nM). Under all conditions and for both muscle types, gl ucose uptake values for mdx and control muscles were similar although heat production was lower in mdx muscles. The marked stimulation of GU P by insulin in both mdx and control muscles had only minor effects on heat production. In contrast, glucose deprivation or inhibition of gl ycolysis with 2-deoxy-D-glucose (5 mM) significantly decreased heat pr oduction in control muscles only, which attenuated, although did not s uppress, the difference in basal heat production between mdx and contr ol muscles. Stimulation of heat production by a short-chain fatty acid salt (octanoate, 2 mM) was significantly less marked in mdx than in c ontrol muscles. Increased cytoplasmic synthesis of CoA by addition of 5 mM pantothenate (vitamin B5) increased the thermogenic response to g lucose more in mdx than in control muscles. We conclude that the low e nergy turnover in mdx-mouse muscle fibres is not due to a decrease of intracellular glucose availability, but rather to a decreased oxidativ e utilization of glucose and free fatty acids. We suggest that some en zyme complex of the tricarboxylic acid cycle or inefficiency of CoA tr ansport in the mitochondria could be involved.