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

Daniel J. Cuthbertson (Lead / Corresponding author), John Babraj, Graham Leese, Mario Siervo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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 [(13)C] leucine during a primed, constant infusion of [1-(13)C] 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, p70(S6k) 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.

Original languageEnglish
Pages (from-to)1716-1719
Number of pages4
JournalClinical Nutrition
Volume36
Issue number6
Early online date25 Nov 2016
DOIs
Publication statusPublished - Dec 2017

Keywords

  • Sarcopenia
  • Obesity
  • Skeletal muscle
  • Insulin resistance
  • Protein synthesis
  • Anabolic resistance

Fingerprint Dive into the research topics of 'Anabolic resistance does not explain sarcopenia in patients with type 2 diabetes mellitus, compared with healthy controls, despite reduced mTOR pathway activity'. Together they form a unique fingerprint.

  • Cite this