Between one- and two-thirds of all alcohol abusers have impairment of muscle function that may be accompanied by biochemical lesions and/or the presence of a defined
myopathy characterised by selective
atrophy of Type II fibres. Perturbations in
protein metabolism are central to the effects on muscle and account for the reductions in muscle mass and fibre diameter.
Ethanol abuse is also associated with abnormalities in
carbohydrate (as well as lipid) metabolism in skeletal muscle.
Ethanol-mediated
insulin resistance is allied with the inhibitory effects of
ethanol on
insulin-stimulated carbohydrate metabolism. It acutely impairs
insulin-stimulated
glucose and lipid metabolism, although it is not known whether it has an analogous effect on
insulin-stimulated
protein synthesis. In
alcoholic cirrhosis,
insulin resistance occurs with respect to carbohydrate metabolism, although the actions of
insulin to suppress protein degradation and stimulate
amino acid uptake are unimpaired. In acute alcohol-dosing studies defective rates of
protein synthesis occur, particularly in Type II fibre-predominant muscles. The relative amounts of
mRNA-encoding
contractile proteins do not appear to be adversely affected by chronic alcohol feeding, although subtle changes in
muscle protein isoforms may occur. There are also rapid and sustained reductions in total (largely
ribosomal) RNA in chronic studies. Loss of
RNA appears to be related to increases in the activities of specific muscle RNases in these long-term studies. However, in acute dosing studies (less than 1 day), the reductions in
muscle protein synthesis are not due to overt loss of total
RNA. These data implicate a role for translational modifications in the initial stages of the
myopathy, although changes in transcription and/or protein degradation may also be superimposed. These events have important implications for whole-body metabolism.