Mechanism of muscle wasting in myotonic dystrophy

Robert C. Griggs, Ralph Jozefowicz, William Kingston, K Sreekumaran Nair, Barbara E. Herr, David Halliday

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Myotonic dystrophy is associated with progressive muscular atrophy. In order to determine the mechanism of muscle wasting in this condition, we measured fractional mixed skeletal muscle protein synthesis in the postabsorptive state in 8 patients with myotonic dystrophy, and compared the results with those of 10 normal subjects. Fractional muscle protein synthesis was determined by measuring the increment of 13C leucine in mixed skeletal muscle protein obtained by needle biopsy from the quadriceps muscle during a primed-continuous infusion of L-(1-13C) leucine. We used plasma 13C α-ketoisocaproate (representing intracellular leucine labeling) as the precursor pool for the calculation of fractional muscle protein synthesis and leucine kinetics. Fractional muscle protein synthesis was depressed in the patients with myotonic dystrophy (28% decrease, p < 0.02). Leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux were not different between the patients with myotonic dystrophy and the normal control subjects. Muscle atrophy in myotonic dystrophy reflects a selective decrease in muscle protein synthesis without any similar decrease in nonmuscle protein synthesis. This decrease may result from an impaired end-organ response to anabolic hormones or substrates.

Original languageEnglish (US)
Pages (from-to)505-512
Number of pages8
JournalAnnals of Neurology
Volume27
Issue number5
StatePublished - May 1990
Externally publishedYes

Fingerprint

Myotonic Dystrophy
Muscle Proteins
Leucine
Muscles
Skeletal Muscle
Spinal Muscular Atrophy
Muscular Atrophy
Quadriceps Muscle
Needle Biopsy
Hormones

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Griggs, R. C., Jozefowicz, R., Kingston, W., Nair, K. S., Herr, B. E., & Halliday, D. (1990). Mechanism of muscle wasting in myotonic dystrophy. Annals of Neurology, 27(5), 505-512.

Mechanism of muscle wasting in myotonic dystrophy. / Griggs, Robert C.; Jozefowicz, Ralph; Kingston, William; Nair, K Sreekumaran; Herr, Barbara E.; Halliday, David.

In: Annals of Neurology, Vol. 27, No. 5, 05.1990, p. 505-512.

Research output: Contribution to journalArticle

Griggs, RC, Jozefowicz, R, Kingston, W, Nair, KS, Herr, BE & Halliday, D 1990, 'Mechanism of muscle wasting in myotonic dystrophy', Annals of Neurology, vol. 27, no. 5, pp. 505-512.
Griggs RC, Jozefowicz R, Kingston W, Nair KS, Herr BE, Halliday D. Mechanism of muscle wasting in myotonic dystrophy. Annals of Neurology. 1990 May;27(5):505-512.
Griggs, Robert C. ; Jozefowicz, Ralph ; Kingston, William ; Nair, K Sreekumaran ; Herr, Barbara E. ; Halliday, David. / Mechanism of muscle wasting in myotonic dystrophy. In: Annals of Neurology. 1990 ; Vol. 27, No. 5. pp. 505-512.
@article{ad8cdc7acf974360913c8c3f7b764608,
title = "Mechanism of muscle wasting in myotonic dystrophy",
abstract = "Myotonic dystrophy is associated with progressive muscular atrophy. In order to determine the mechanism of muscle wasting in this condition, we measured fractional mixed skeletal muscle protein synthesis in the postabsorptive state in 8 patients with myotonic dystrophy, and compared the results with those of 10 normal subjects. Fractional muscle protein synthesis was determined by measuring the increment of 13C leucine in mixed skeletal muscle protein obtained by needle biopsy from the quadriceps muscle during a primed-continuous infusion of L-(1-13C) leucine. We used plasma 13C α-ketoisocaproate (representing intracellular leucine labeling) as the precursor pool for the calculation of fractional muscle protein synthesis and leucine kinetics. Fractional muscle protein synthesis was depressed in the patients with myotonic dystrophy (28{\%} decrease, p < 0.02). Leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux were not different between the patients with myotonic dystrophy and the normal control subjects. Muscle atrophy in myotonic dystrophy reflects a selective decrease in muscle protein synthesis without any similar decrease in nonmuscle protein synthesis. This decrease may result from an impaired end-organ response to anabolic hormones or substrates.",
author = "Griggs, {Robert C.} and Ralph Jozefowicz and William Kingston and Nair, {K Sreekumaran} and Herr, {Barbara E.} and David Halliday",
year = "1990",
month = "5",
language = "English (US)",
volume = "27",
pages = "505--512",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "5",

}

TY - JOUR

T1 - Mechanism of muscle wasting in myotonic dystrophy

AU - Griggs, Robert C.

AU - Jozefowicz, Ralph

AU - Kingston, William

AU - Nair, K Sreekumaran

AU - Herr, Barbara E.

AU - Halliday, David

PY - 1990/5

Y1 - 1990/5

N2 - Myotonic dystrophy is associated with progressive muscular atrophy. In order to determine the mechanism of muscle wasting in this condition, we measured fractional mixed skeletal muscle protein synthesis in the postabsorptive state in 8 patients with myotonic dystrophy, and compared the results with those of 10 normal subjects. Fractional muscle protein synthesis was determined by measuring the increment of 13C leucine in mixed skeletal muscle protein obtained by needle biopsy from the quadriceps muscle during a primed-continuous infusion of L-(1-13C) leucine. We used plasma 13C α-ketoisocaproate (representing intracellular leucine labeling) as the precursor pool for the calculation of fractional muscle protein synthesis and leucine kinetics. Fractional muscle protein synthesis was depressed in the patients with myotonic dystrophy (28% decrease, p < 0.02). Leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux were not different between the patients with myotonic dystrophy and the normal control subjects. Muscle atrophy in myotonic dystrophy reflects a selective decrease in muscle protein synthesis without any similar decrease in nonmuscle protein synthesis. This decrease may result from an impaired end-organ response to anabolic hormones or substrates.

AB - Myotonic dystrophy is associated with progressive muscular atrophy. In order to determine the mechanism of muscle wasting in this condition, we measured fractional mixed skeletal muscle protein synthesis in the postabsorptive state in 8 patients with myotonic dystrophy, and compared the results with those of 10 normal subjects. Fractional muscle protein synthesis was determined by measuring the increment of 13C leucine in mixed skeletal muscle protein obtained by needle biopsy from the quadriceps muscle during a primed-continuous infusion of L-(1-13C) leucine. We used plasma 13C α-ketoisocaproate (representing intracellular leucine labeling) as the precursor pool for the calculation of fractional muscle protein synthesis and leucine kinetics. Fractional muscle protein synthesis was depressed in the patients with myotonic dystrophy (28% decrease, p < 0.02). Leucine flux, leucine oxidation, and the nonoxidative portion of leucine flux were not different between the patients with myotonic dystrophy and the normal control subjects. Muscle atrophy in myotonic dystrophy reflects a selective decrease in muscle protein synthesis without any similar decrease in nonmuscle protein synthesis. This decrease may result from an impaired end-organ response to anabolic hormones or substrates.

UR - http://www.scopus.com/inward/record.url?scp=0025269154&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025269154&partnerID=8YFLogxK

M3 - Article

VL - 27

SP - 505

EP - 512

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 5

ER -