Effect of starvation on human muscle protein metabolism and its response to insulin
- Yale Univ. School of Medicine, New Haven, CT (USA)
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 approximately 25 muU/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 less than 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 less than 0.05); this effect was mediated exclusively by accelerated local rates of amino acid appearance (Ra), with no reduction in rates of disposal (Rd). Local hyperinsulinemia in the postabsorptive condition caused a twofold increase in forearm glucose uptake (P less than 0.01) and completely suppressed the net forearm output of Phe and Leu (P less than 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 approximately 40% suppression of Ra (P less than 0.02) rather than a stimulation of Rd. 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.
- OSTI ID:
- 6170950
- Journal Information:
- American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 259:4 Pt 1; ISSN 0002-9513; ISSN AJPHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINO ACIDS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
FASTING
GLUCOSE
HEXOSES
HORMONES
HYDROGEN COMPOUNDS
INSULIN
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LEUCINE
METABOLISM
MONOSACCHARIDES
MUSCLES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PHENYLALANINE
REACTION KINETICS
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS