Mechanism of insulin's anabolic effect on muscle: Measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures

Lisa S. Chow, Robert C. Albright, Maureen L. Bigelow, Gianna Toffolo, Claudio Cobelli, K Sreekumaran Nair

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Despite being an anabolic hormone in skeletal muscle, insulin's anticatabolic mechanism in humans remains controversial, with contradictory reports showing either stimulation of protein synthesis (PS) or inhibition of protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of aminoacyl-tRNA and intracellular pools. We report that insulin's effect on muscle protein turnover using aminoacyl-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 3 h, 10 subjects received a 4-h femoral arterial infusion of insulin (0.125 mU·kg-1·min-1), 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 AA-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume291
Issue number4
DOIs
StatePublished - 2006

Fingerprint

Anabolic Agents
Muscle Proteins
Insulin
Transfer RNA
Muscle
Muscles
Amino Acid-Specific Transfer RNA
Phenylalanine
Leucine
Proteins
RNA Precursors
Amino Acids
Protein Precursors
Thigh
Metabolism
Healthy Volunteers
Skeletal Muscle
Hormones
Tissue
Plasmas

Keywords

  • Amino acids
  • Leucine
  • Phenylalanine
  • Stable isotopes

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Mechanism of insulin's anabolic effect on muscle : Measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures. / Chow, Lisa S.; Albright, Robert C.; Bigelow, Maureen L.; Toffolo, Gianna; Cobelli, Claudio; Nair, K Sreekumaran.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 291, No. 4, 2006.

Research output: Contribution to journalArticle

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AB - Despite being an anabolic hormone in skeletal muscle, insulin's anticatabolic mechanism in humans remains controversial, with contradictory reports showing either stimulation of protein synthesis (PS) or inhibition of protein breakdown (PB) by insulin. Earlier measurements of muscle PS and PB in humans have relied on different surrogate measures of aminoacyl-tRNA and intracellular pools. We report that insulin's effect on muscle protein turnover using aminoacyl-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 3 h, 10 subjects received a 4-h femoral arterial infusion of insulin (0.125 mU·kg-1·min-1), 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 AA-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.

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