Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin

Tissue-Specific Regulation of Mitochondrial and Cytoplasmic Protein Synthesis Rates by Insulin Yves Boirie , Kevin R. Short , Bo Ahlman , Michael Charlton and K. Sreekumaran Nair Division of Endocrinology and Metabolism, Mayo Clinic and Foundation, Rochester, Minnesota Abstract In vivo studies have reported conflicting effects of insulin on mixed tissue protein synthesis rates. To test the hypothesis that insulin has differential effects on synthesis rates of various protein fractions in different organs, we infused miniature swine ( n = 8 per group) with saline, insulin alone (at 0.7 mU/kg −1 · min −1 ), or insulin plus an amino acid mixture for 8 h. Fractional synthesis rate (FSR) of mitochondrial and cytoplasmic proteins in liver, heart, and skeletal muscle, as well as myosin heavy chain (MHC) in muscle, were measured using l -[1- 13 C]leucine as a tracer. The FSR of mitochondrial and cytoplasmic proteins were highest in liver, followed by heart and then muscle. Mitochondrial FSR in muscle was higher during insulin and insulin plus amino acid infusions than during saline. Insulin had no significant effect on FSR of MHC in muscle. In contrast, FSR of both mitochondrial and cytoplasmic proteins were not stimulated by insulin in liver. Insulin also did not increase FSR of mitochondrial in heart, whereas insulin and amino acid stimulated FSR of cytoplasmic protein. In conclusion, insulin stimulates the synthesis of muscle mitochondrial proteins, with no significant stimulatory effect on synthesis of sarcoplasmic and MHC. These results demonstrate that insulin has different effects on synthesis rates of specific protein fractions in the liver, heart, and skeletal muscle. Footnotes Address correspondence and reprint requests to K. Sreekumaran Nair, Endocrine Research Unit, Mayo Clinic and Foundation, 200 First St. SW, Room 5-194 Joseph, Rochester, MN 55905. E-mail: nair.sree{at}mayo.edu . Received for publication 10 November 2000 and accepted in revised form 4 September 2001. AA, group treated with amino acid; ANOVA, analysis of variance; BCAA, branched-chain amino acids; FSR, fractional synthesis rate; GC-MS, gas chromatograph–mass spectrometer; INS, group treated with insulin; INS+AA, group treated with insulin plus amino acid; KIC, ketoisocaproate; MHC, myosin heavy chain; S, group treated with saline.