Skip to main page content

• HOME
• Current Issue
• Email Alerts
• Archives
• Subscriptions
• Search for Articles

This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 90/5/1343    most recent ajcn.2009.27543v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wilkes, E. A Articles by Rennie, M. J Search for Related Content PubMed PubMed Citation Articles by Wilkes, E. A Articles by Rennie, M. J Agricola Articles by Wilkes, E. A Articles by Rennie, M. J

Blunting of insulin inhibition of proteolysis in legs of older subjects may contribute to age-related sarcopenia^1,2,3

¹ From the University of Nottingham, School of Graduate Entry Medicine and Health, Derby, United Kingdom (EAW, ALS, PJA, RP, DR, KS, and MJR).

² Supported by grants from UK BBSRC (BB/X510697/1, BB/X510697/1, and BB/C516779/1) and from the EC EXEGENESIS program.

³ Address reprint requests and correspondence to MJ Rennie, University of Nottingham, School of Graduate Entry Medicine and Health, Derby City Hospital, Uttoxeter Road, Derby DE22 3DT, United Kingdom. E-mail: michael.rennie{at}nottingham.ac.uk.

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 120 µmol/L) clamp procedures at plasma insulin concentrations of 5 and 15 µIU/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 D₅-phenylalanine and [1,2-¹³C₂]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 · 100 mL leg^–1 · min^–1 and 30 ± 5 compared with 24 ± 4 nmol phenylalanine · 100 mL leg^–1 · min^–1 in young and older groups, respectively). However, although insulin at 15 µIU/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.

This article has been cited by other articles:

				M. V. Narici and N. Maffulli Sarcopenia: characteristics, mechanisms and functional significance Br. Med. Bull., September 1, 2010; 95(1): 139 - 159. [Abstract] [Full Text] [PDF]

				S. Perrini, L. Laviola, M. C. Carreira, A. Cignarelli, A. Natalicchio, and F. Giorgino The GH/IGF1 axis and signaling pathways in the muscle and bone: mechanisms underlying age-related skeletal muscle wasting and osteoporosis J. Endocrinol., June 1, 2010; 205(3): 201 - 210. [Abstract] [Full Text] [PDF]

				C. A. Greig, P. J. Atherton, and M. J. Rennie Can an NSAID a day keep muscle wasting away? J. Physiol., December 15, 2009; 587(24): 5799 - 5800. [Full Text] [PDF]