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Am J Clin Nutr. 2009 Nov;90(5):1343-50. doi: 10.3945/ajcn.2009.27543. Epub 2009 Sep 9.

Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia.

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1
University of Nottingham, School of Graduate Entry Medicine and Health, Derby, United Kingdom.

Abstract

BACKGROUND:

Reduced postprandial muscle proteolysis is mainly due to increased insulin availability. Whether rates of proteolysis in response to low physiologic doses of insulin are affected by aging is unknown.

OBJECTIVES:

We tested the hypothesis that suppression of leg protein breakdown (LPB) by insulin is blunted in older subjects, together with blunted activation of Akt-protein kinase B (PKB).

DESIGN:

Groups of 8 young [mean (+/-SD) age: 24.5 +/- 1.8 y] and older (65.0 +/- 1.3 y) participants were studied during euglycemic (5 mmol/L), isoaminoacidemic (blood leucine approximately 120 micromol/L) clamp procedures at plasma insulin concentrations of approximately 5 and approximately 15 microIU/mL for 1.5 h. Leg amino acid balance, whole-leg protein turnover (as dilution of amino acid tracers), and muscle protein synthesis were measured with D(5)-phenylalanine and [1,2-(13)C(2)]leucine. The kinase activity of muscle Akt-PKB and the extent of phosphorylation of signaling proteins associated with the mTOR (mammalian target of rapamycin) pathway were measured before and after the clamp procedures.

RESULTS:

Basal LPB rates were not different between groups (66 +/- 11 compared with 51 +/- 10 nmol leucine x 100 mL leg(-1) x min(-1) and 30 +/- 5 compared with 24 +/- 4 nmol phenylalanine x 100 mL leg(-1) x min(-1) in young and older groups, respectively). However, although insulin at approximately 15 microIU/mL lowered LPB by 47% in the young subjects (P < 0.05) and abolished the negative leg amino acid balance, this caused only a 12% fall (P > 0.05) in the older group. Akt-PKB activity mirrored decreases in LPB. No differences were seen in muscle protein synthesis or associated anabolic signaling phosphoproteins.

CONCLUSIONS:

At moderate availability, the effect of insulin on LPB is diminished in older human beings, and this effect may be mediated through blunted Akt-PKB activation.

PMID:
19740975
DOI:
10.3945/ajcn.2009.27543
[Indexed for MEDLINE]
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