Effect of insulin on amino acid uptake and protein turnover in skeletal muscle from septic rats. Evidence for insulin resistance of protein breakdown

P. O. Hasselgren, B. W. Warner, J. H. James, H. Takehara and J. E. Fischer

We investigated the effect of different concentrations of insulin (0, 10, 1 X 10(2), 1 X 10(3), 1 X 10(4), and 1 X 10(5) mU/L [0, 70, 7 X 10(2), 7 X 10(3), 7 X 10(4), and 7 X 10(5) pmol/L]) on amino acid (alpha-aminoisobutyric acid) uptake and protein synthesis and breakdown in incubated extensor digitorum longus (EDL) and soleus muscles of rats. We studied three groups: untreated, fed rats; sham-operated rats; and septic rats. Sepsis was induced by cecal ligation and puncture. The alpha-aminoisobutyric acid uptake was increased by insulin in all three groups. Protein synthesis was maximally stimulated by 30% to 40% by 1 X 10(2) mU/L (7 X 10(2) pmol/L) of insulin in all three groups. Protein degradation in soleus muscle was not affected by insulin. In EDL muscles from untreated and sham-operated rats, protein breakdown was reduced by 15% to 20% by 1 X 10(2) mU/L (7 X 10(2) pmol/L) of insulin. In contrast, protein breakdown was not inhibited by insulin in septic EDL muscle until the concentration of the hormone was increased to 1 X 10(4) mU/L (7 X 10(4) pmol/L), at which concentration the hormonal effect was less than half that in nonseptic muscle. The results suggest a postreceptor insulin resistance of protein breakdown in septic muscle, while the response to the hormone of amino acid transport and protein synthesis was not altered in sepsis.

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