Effect of Insulin on Amino Acid Uptake and Protein Turnover in Skeletal Muscle From Septic Rats: Evidence for Insulin Resistance of Protein Breakdown

• We investigated the effect of different concentrations of insulin (0, 10, 1×10², 1×10³, 1×10⁴, and 1×10⁵ mU/L [0, 70, 7×10², 7×10³, 7×10⁴, and 7×10⁵ pmol/L]) on amino acid (α-aminoisobutyric acid) uptake and protein synthesis and breakdown in incubated extensor digitorum longus (EDL) and soleus muscles of rats. We studied three groups: (1) untreated, fed rats; (2) sham-operated rats; and (3) septic rats. Sepsis was induced by cecal ligation and puncture. The α-aminoisobutyric acid uptake was increased by insulin in all three groups. Protein synthesis was maximally stimulated by 30% to 40% by 1×10² mU/L (7×10² 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 × 10² mU/L (7×10² 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 ×10⁴ mU/L (7×10⁴ 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.