Acute effects of phorbol esters on the protein-synthetic rate and carbohydrate metabolism of normal and mdx mouse muscles.
1. mdx mice do not express dystrophin, the product of the gene which is defective in Duchenne and Becker muscular dystrophy. We have previously shown that protein-synthetic rates (ks) are increased in mdx mouse muscles [MacLennan & Edwards (1990) Biochem. J. 268, 795-797]. 2. The tumour-promoting stereoisomer of phorbol 12,13-didecanoate (4 beta-PDD) acutely increased the ks of muscles from mdx and wild-type (C57BL/10) mice incubated in vitro in the absence of insulin. The effects of 4 beta-PDD are presumably mediated by activation of protein kinase C (PKC). 3. The muscle glycogen concentrations of mdx mice were higher than those of C57BL/10 mice. Studies performed in vivo and in vitro suggested that the effect might be at least partially due to increased rate of glycogen synthesis in mdx muscle. 4. 4 beta-PDD increased the glycogen-synthetic rates rates of C57BL/10, but not mdx, muscles incubated in vitro in the absence of insulin. 5. In muscles from both species incubated in the absence of insulin, treatment with 4 beta-PDD also induced increased rates of glucose uptake and lactate production. Kinetic studies of C57BL/10 and mdx muscles suggested that 4 beta-PDD raised the Vmax. of glucose uptake, but did not alter the Km for the process. 6. The possible role of PKC in controlling the protein and carbohydrate metabolism of normal and mdx mouse muscles is discussed.
MacLennan
P A
PA
Department of Medicine, University of Liverpool, U.K.
McArdle
A
A
Edwards
R H
RH
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012016:Reference Values
D007328:Insulin; D007773:Lactates; D010703:Phorbol Esters; C008876:phorbol-12,13-didecanoate; D006003:Glycogen; D005947:Glucose