Daniel J Cuthbertson1, John Babraj2, Graham Leese3, Mario Siervo4. 1. Medical Research Council-Arthritis UK Centre of Excellence for Musculoskeletal Ageing Research, University of Liverpool, L69 3GA, UK. Electronic address: daniel.cuthbertson@liverpool.ac.uk. 2. University of Abertay, Dundee, Scotland, UK. 3. Department of Diabetes, Ninewells Hospital and Medical School, Dundee, Scotland, UK. 4. Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Campus for Ageing and Vitality, Newcastle on Tyne, NE4 5PL, UK.
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 [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.
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 obesemen 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.
Authors: Drew E Gonzalez; Matthew J McAllister; Hunter S Waldman; Arny A Ferrando; Jill Joyce; Nicholas D Barringer; J Jay Dawes; Adam J Kieffer; Travis Harvey; Chad M Kerksick; Jeffrey R Stout; Tim N Ziegenfuss; Annette Zapp; Jamie L Tartar; Jeffery L Heileson; Trisha A VanDusseldorp; Douglas S Kalman; Bill I Campbell; Jose Antonio; Richard B Kreider Journal: J Int Soc Sports Nutr Date: 2022-06-23 Impact factor: 4.948