Effect of starvation on human muscle protein metabolism and its response to insulin

D. A. Fryburg, E. J. Barrett, Rita Jean Louard, R. A. Gelfand

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Although starvation is known to impair insulin-stimulated glucose disposal, whether it also induces resistance to insulin's antiproteolytic action in muscle is unknown. To assess the effect of fasting on muscle protein turnover in the basal state and in response to insulin, we measured forearm amino acid kinetics, using [3H]phenylalanine (Phe) and [14C]leucine (Leu) infused systemically, in eight healthy subjects after 12 (postabsorptive) and 60 h of fasting. After a 150-min basal period, forearm local insulin concentration was selectively raised by ~ 25 μU/ml for 150 min by intra-arterial insulin infusion (0.02 mU · kg-1 · min-1). The 60-h fast increased urine nitrogen loss and whole body Leu flux and oxidation (by 50-75%, all P < 0.02). Post-absorptively, forearm muscle exhibited a net release of Phe and Leu, which increased two- to threefold after the 60-h fast (P < 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (R(a)), with no reduction in rates of disposal (R(d)). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P < 0.01) and completely suppressed the net forearm output of Phe and Leu (P < 0.02). After the 60-h fast, forearm glucose disposal was depressed basally and showed no response to insulin; in contrast, insulin totally abolished the accelerated net forearm release of Phe and Leu. The action of insulin to reverse the augmented net release of Phe and Leu was mediated exclusively by a ~ 40% suppression of R(a) (P < 0.02) rather than a stimulation of R(d). We conclude that in short-term fasted humans 1) muscle amino acid output accelerates due to increased proteolysis rather than reduced protein synthesis, and 2) despite its catabolic state and a marked impairment in insulin-mediated glucose disposal, muscle remains sensitive to insulin's antiproteolytic action.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume259
Issue number4 22-4
StatePublished - 1990
Externally publishedYes

Fingerprint

Muscle Proteins
Starvation
Metabolism
Forearm
Leucine
Insulin
Phenylalanine
Muscle
Glucose
Muscles
Amino Acids
Fasting
Proteolysis
Intra Arterial Infusions
Hyperinsulinism
Insulin Resistance
Healthy Volunteers
Nitrogen
Urine
Fluxes

Keywords

  • amino acid tracer kinetics
  • leucine
  • phenylalanine

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

Effect of starvation on human muscle protein metabolism and its response to insulin. / Fryburg, D. A.; Barrett, E. J.; Louard, Rita Jean; Gelfand, R. A.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 259, No. 4 22-4, 1990.

Research output: Contribution to journalArticle

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