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Mechanism of Insulin's Anabolic Effect on Muscle - Measurements of Muscle Protein Synthesis and Breakdown Using Aminoacyl tRNA and Other Surrogate Measures.
Chow LS, Albright RC, Bigelow ML, Toffolo G, Cobelli C, Nair KS.
Division of Endocrinology, Nutrition and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota, United States.
Despite being an anabolic hormone in skeletal muscle, insulin's anti-catabolic mechanism in humans remains controversial with contradictory reports showing either stimulation protein synthesis (PS) or inhibition protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of amino acyl tRNA and intracellular pool. We report insulin's effect on muscle protein turnover using amino acyl-tRNA as the precursor of PS and PB is calculated by mass balance of tracee amino acid (AA). We compared the results calculated from various surrogate measures. To determine the physiological role of insulin on muscle protein metabolism we infused tracers of leucine and phenylalanine into 18 healthy subjects and after a three hours, 10 subjects received a four hour femoral arterial infusion of insulin (0.125 mU/kg/min) while eight subjects continued with saline. Tracer to tracee ratios of leucine, phenylalanine and ketoisocaproate were measured in the arterial and venous plasma, muscle tissue fluid and AA-tRNA to calculate muscle PB and PS. Insulin infusion, unlike saline, significantly reduced the efflux of leucine and phenylalanine from muscle bed based on various surrogate measures which agreed with those based on leucyl-tRNA (-28%) indicating a reduction in muscle PB (P<0.02) without any significant effect on muscle PS. In conclusion, using amino-acyl tRNA as the precursor pool, it is demonstrated that in healthy humans in the postabsorptive state, insulin does not stimulate muscle protein synthesis and confirmed that insulin achieves muscle protein anabolism by inhibition of muscle protein breakdown.
Chow LS, Albright RC, Bigelow ML, Toffolo G, Cobelli C, Nair KS.
Division of Endocrinology, Nutrition and Metabolism, Mayo Clinic College of Medicine, Rochester, Minnesota, United States.
Despite being an anabolic hormone in skeletal muscle, insulin's anti-catabolic mechanism in humans remains controversial with contradictory reports showing either stimulation protein synthesis (PS) or inhibition protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of amino acyl tRNA and intracellular pool. We report insulin's effect on muscle protein turnover using amino acyl-tRNA as the precursor of PS and PB is calculated by mass balance of tracee amino acid (AA). We compared the results calculated from various surrogate measures. To determine the physiological role of insulin on muscle protein metabolism we infused tracers of leucine and phenylalanine into 18 healthy subjects and after a three hours, 10 subjects received a four hour femoral arterial infusion of insulin (0.125 mU/kg/min) while eight subjects continued with saline. Tracer to tracee ratios of leucine, phenylalanine and ketoisocaproate were measured in the arterial and venous plasma, muscle tissue fluid and AA-tRNA to calculate muscle PB and PS. Insulin infusion, unlike saline, significantly reduced the efflux of leucine and phenylalanine from muscle bed based on various surrogate measures which agreed with those based on leucyl-tRNA (-28%) indicating a reduction in muscle PB (P<0.02) without any significant effect on muscle PS. In conclusion, using amino-acyl tRNA as the precursor pool, it is demonstrated that in healthy humans in the postabsorptive state, insulin does not stimulate muscle protein synthesis and confirmed that insulin achieves muscle protein anabolism by inhibition of muscle protein breakdown.
