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Insulin’s Effect on Synthesis Rates of Liver Proteins

A Swine Model Comparing Various Precursors of Protein Synthesis

Endocrine Research Unit, Division of Endocrinology and Metabolism, Mayo Clinic and Foundation, Rochester, Minnesota

Insulin’s effect on the synthesis of liver proteins remains to be fully defined. Previous studies using various surrogate measures of amino acyl–tRNA have reported variable results of insulin’s effect on liver protein synthesis. We determined the effect of insulin with or without amino acid supplementation on the synthesis rates of liver proteins (tissue, albumin, and fibrinogen) using L-[1-¹³C]Leu as a tracer in 24 male miniature swine. In addition, we compared the isotopic enrichment of different precursors of liver proteins with that of amino acyl-tRNA using L-[1-¹³C]Leu and L-[¹⁵N]Phe as tracers. Although liver tissue fluid enrichment of [¹³C]Leu and [¹⁵N]Phe and that of plasma [¹³C]ketoisocaproatic acid (KIC) were very similar to that of tRNA, plasma isotopic enrichment of both Leu and Phe were substantially higher (P < 0.01) and VLDL apolipoprotein-B₁₀₀ enrichment was lower (P < 0.01) than the respective amino acyl-tRNA enrichment. Plasma KIC enrichment most accurately predicted leucyl-tRNA enrichment, whereas plasma Leu enrichment was best correlated with that of tRNA. Neither insulin alone nor insulin plus amino acid infusion had an effect on liver tissue protein synthesis. In contrast, insulin alone decreased the albumin synthesis rate, and insulin with amino acids maintained the albumin synthesis rate. Insulin with or without amino acids inhibited the fibrinogen synthesis rate. These results, based on synthetic rates using amino acyl–tRNA, were consistent with those obtained using KIC or tissue fluid Leu or Phe as precursor pools. These studies demonstrated that plasma KIC enrichment is a convenient and reliable surrogate measure of leucyl-tRNA in liver. We also concluded that insulin has differential effects on the synthesis rates of liver proteins. Whereas insulin with or without amino acid supplement has no acute effect on the synthesis of liver tissue protein, insulin has a substantial inhibitory effect on fibrinogen synthesis. In contrast, insulin administration along with amino supplement is necessary to maintain albumin synthesis rate.

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