Physiological hyperinsulinemia inhibits myocardial protein degradation in vivo in the canine heart

Abstract

Myocardial protein turnover in vivo was examined in anesthetized dogs following a 16- or 36-hour fast and again during a hyperinsulinemic (2 mU/kg per minute) euglycemic clamp with or without amino acid replacement or during saline infusion. We measured myocardial phenylalanine balance and rates of protein synthesis and degradation, using the extraction of intravenously infused L-[ring-2,6-3H] phenylalanine and the dilution of its specific activity across the heart at isotopic steady state. After both a 16-hour (n=19) and 36-hour fast (n=10), there was net myocardial release of phenylalanine indicated by the negative balances for phenylalanine of -52±9 (p<0.001) and -38±9 (p<0.005) nmol/min, respectively. Overall, the basal rate of myocardial protein degradation was lower in the 36-hour-fasted animals (81±13 versus 121±12 nmol/min, p<0.05). Myocardial phenylalanine balance and rates of protein synthesis and degradation did not change during insulin and glucose infusion in the 36-hour-fasted animals (n=10). In these animals, there was a 30-40% decline in plasma amino acid concentrations, including branched chain (p<0.001) and essential amino acids (p<0.001). In the 16-hour-fasted animals receiving an infusion of amino acids during the euglycemic clamp (n=11), myocardial phenylalanine balance shifted from negative to neutral (from -40±6 to 6±15 nmol/min, p<0.05) because of a 50% inhibition of heart protein degradation (from 118±12 to 60±7 nmol/min, p<0.001); heart protein synthesis was unchanged. In the additional 16-hour-fasted animals receiving saline (n=8), the net negative myocardial phenylalanine balance persisted throughout the infusion. These results demonstrate that physiological increments in plasma insulin have a relatively anabolic effect on myocardial protein turnover in vivo caused by inhibition of protein degradation. Furthermore, hypoaminoacidemia appears to blunt insulin's anabolic action on heart muscle.