Regulation by insulin of muscle protein metabolism during sepsis and other catabolic conditions.

The anabolic effect of insulin in skeletal muscle reflects increased protein synthesis and reduced protein degradation. Insulin stimulates protein synthesis mainly at the translational level by enhancing peptide chain initiation. The mechanism by which the hormone reduces protein breakdown is less well understood, but inhibition of the lysosomal pathway is probably an important component. Sepsis results in pronounced muscle catabolism, mainly reflecting increased protein breakdown, particularly myofibrillar protein breakdown, and a less prominent inhibition of protein synthesis. There is evidence that muscle protein breakdown becomes resistant to the effect of insulin during sepsis, probably at the postreceptor level. This insulin resistance may be mediated by increased beta-adrenoreceptor activity. In contrast, the stimulatory effect of insulin on muscle protein synthesis and amino acid transport is maintained during sepsis. The regulatory effect of insulin on muscle protein metabolism may be affected by other catabolic conditions as well, e.g., fasting, denervation, burn injury, and trauma.