Mechanism of insulin's anabolic effect on muscle: measurements of muscle protein synthesis and breakdown using aminoacyl-tRNA and other surrogate measures.
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 mUxkg(-1)xmin(-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.
Chow
Lisa S
LS
Division of Endocrinology, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA.
Albright
Robert C
RC
Bigelow
Maureen L
ML
Toffolo
Gianna
G
Cobelli
Claudio
C
Nair
K Sreekumaran
KS
D000328:Adult; D044963:Biopsy, Fine-Needle; D002250:Carbon Radioisotopes; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D007930:Leucine / Q000097:blood / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009587:Nitrogen Isotopes; D010649:Phenylalanine / Q000097:blood / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012356:RNA, Transfer, Leu / Q000378:metabolism; D012360:RNA, Transfer, Phe / Q000378:metabolism
D002250:Carbon Radioisotopes; D007328:Insulin; D009124:Muscle Proteins; D009587:Nitrogen Isotopes; D012356:RNA, Transfer, Leu; D012360:RNA, Transfer, Phe; D010649:Phenylalanine; D007930:Leucine