Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity

Babraj, John; Cuthbertson, Daniel J.; Leese, Graham; Siervo, Mario

Abstract

© 2016 Background Ageing and type 2 diabetes mellitus (T2DM) are risk factors for skeletal muscle loss. We investigated whether anabolic resistance to feeding might underlie accelerated muscle loss in older people with T2DM and whether dysregulated mTOR signalling was implicated. Subjects 8 obese men with T2DM, and 12 age-matched controls were studied (age 68 ± 3 vs. 68±6 y; BMI: 30 ± 2 vs. 27 ± 5 kg m−2). Methods Body composition was measured by dual-X-ray absorptiometry. Insulin and glucose were clamped at post-absorptive concentrations (13 ± 2 vs. 9 ± 3 mU l−1; 7.4 ± 1.9 vs. 4.6 ± 0.4 mmol l−1; T2DM vs. controls). Fractional synthetic rates (FSR) of myofibrillar and sarcoplasmic proteins were measured as the rate of incorporation of [13C] leucine during a primed, constant infusion of [1–13C] α-ketoisocaproic acid, 3 h after 10 or 20 g of essential amino acids (EAA) were orally administered. Protein expression of total and phosphorylated mTOR signalling proteins was determined by Western blot analysis. Results Despite a significantly lower appendicular lean mass index and a greater fat mass index in T2DM vs. controls, basal myofibrillar and sarcoplasmic and post-prandial myofibrillar FSR were similar. After 20 g EAA, stimulation of sarcoplasmic FSR was slightly blunted in T2DM patients. Furthermore, feeding 20 g EAA increased phosphorylation of mTOR, p70S6k and 4E-BP1 by 60–100% in controls with no response observed in T2DM. Conclusions There was clear dissociation between changes in mTOR signalling versus changes in protein synthesis rates. However, the intact anabolic response of myofibrillar FSR to feeding in both groups suggests anabolic resistance may not explain accelerated muscle loss in T2DM.

Citation

Babraj, J., Cuthbertson, D. J., Leese, G., & Siervo, M. (2017). Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity. Clinical Nutrition, 36(6), 1716-1719. https://doi.org/10.1016/j.clnu.2016.11.012

• Journal Article Type: Article
• Acceptance Date: Nov 11, 2016
• Online Publication Date: Nov 25, 2016
• Publication Date: Dec 1, 2017
• Deposit Date: Nov 20, 2019
• Publicly Available Date: May 19, 2020
• Journal: Clinical Nutrition
• Print ISSN: 0261-5614
• Electronic ISSN: 1532-1983
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 36
• Issue: 6
• Pages: 1716-1719
• DOI: https://doi.org/10.1016/j.clnu.2016.11.012
• Keywords: Nutrition and Dietetics; Critical Care and Intensive Care Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/3344703
• Publisher URL: https://www.clinicalnutritionjournal.com/article/S0261-5614(16)31328-0/fulltext
• Additional Information: This article is maintained by: Elsevier; Article Title: Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity; Journal Title: Clinical Nutrition; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.clnu.2016.11.012; Content Type: article; Copyright: © 2016 Published by Elsevier Ltd.