Integrin-associated ILK and PINCH1 protein content are reduced in skeletal muscle of maintenance haemodialysis patients

Key points: Patients with renal failure undergoing maintenance haemodialysis are associated with insulin resistance and protein metabolism dysfunction. Novel research suggests that disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in haemodialysis. ILK, PINCH1 and pFAKTyr397 were significantly decreased in haemodialysis compared to controls, whereas Rac1 and Akt2 showed no different between groups. Rac1 deletion in the Rac1 knockout model did not alter the expression of integrin-associated proteins. Phenylalanine kinetics were reduced in the haemodialysis group at 30 and 60 min post meal ingestion compared to controls; both groups showed similar levels of insulin sensitivity and β-cell function. Key proteins in the integrin–cytoskeleton linkage are reduced in haemodialysis patients, suggesting for the first time that integrin-associated proteins dysfunction may contribute to reduced phenylalanine flux without affecting insulin resistance in haemodialysis patients. Abstract: Muscle atrophy, insulin resistance and reduced muscle phosphoinositide 3-kinase-Akt signalling are common characteristics of patients undergoing maintenance haemodialysis (MHD). Disruption to the transmembrane protein linkage between the cytoskeleton and the extracellular matrix in skeletal muscle may contribute to reduced amino acid metabolism and insulin resistance in MHD patients. Eight MHD patients (age: 56 ± 5 years: body mass index: 32 ± 2 kg m–2) and non-diseased controls (age: 50 ± 2 years: body mass index: 31 ± 1 kg m–2) received primed continuous l-[ring-2H5]phenylalanine before consuming a mixed meal. Phenylalanine metabolism was determined using two-compartment modelling. Muscle biopsies were collected prior to the meal and at 300 min postprandially. In a separate experiment, skeletal muscle tissue from muscle-specific Rac1 knockout (Rac1 mKO) was harvested to investigate whether Rac1 depletion disrupted the cytoskeleton-integrin linkage, allowing for cross-model examination of proteins of interest. ILK, PINCH1 and pFAKTyr397 were significantly lower in MHD (P

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Potato Ingestion as an Effective Race Fuel Alternative to Improve Cycling Performance in Trained Cyclists

Carbohydrate (CHO) ingestion is an established strategy to improve endurance performance. Race fuels should not only sustain performance, but also be readily digested and absorbed and replenish electrolytes. Potatoes are a cost-effective option that fulfills these criteria; however, their impact on endurance performance remains unexamined. PURPOSE: Compare the effects of potato purée (POT) ingestion during endurance cycling on subsequent performance versus commercial CHO gel (GEL) or a control (water, CTL). METHODS: Twelve trained cyclists (31±9y; 71±8kg; VO2max: 61±9mL/kg/min) consumed a standardized breakfast then performed a 2h cycling challenge (60-85%VO2max) followed by a time trial (6kJ/kg body mass) while consuming POT, GEL, or CTL in a randomized-crossover design. POT, GEL and CTL were administered with U-[13C6]glucose for an indirect estimate of gastric emptying rate. Repeated blood samples were collected. RESULTS: Time trial performance significantly improved (P=0.03) with POT (33.0±4.5min) and GEL (33.0±4.2min) versus CTL condition (39.5±7.9min); while POT and GEL conditions (P=1.00) had no difference. Post-challenge, blood glucose concentrations were lower (P0.05). CONCLUSION: Potatoes served as a viable alternative to commercial gels by sustaining performance and blood glucose concentrations during endurance cycling events in trained cyclists

Time-dependent regulation of postprandial muscle protein synthesis rates after milk protein ingestion in young men

The anabolic action of “fast” whey protein on the regulation of postprandial muscle protein synthesis has been established to be short-lived in healthy young adults. We assessed the time course of anabolic signaling activation and stimulation of myofibrillar protein synthesis rates (MPS) after ingestion of a food source that represents a more typical meal-induced pattern of aminoacidemia. Seven young men (age: 22 ± 1 y) underwent repeated blood and biopsy sampling during primed, continuous l-[ring-2H5]phenylalanine and l-[1-13C]leucine tracer infusions and ingested 38 g of l-[1-13C]phenylalanine- and l-[1-13C]leucine-labeled milk protein concentrate. A total of ∼27 ± 4 (∼10 g) and ∼31 ± 1% (∼12 g) of dietary protein-derived amino acids were released in circulation between 0 and 120 min and 120–300 min, respectively, of the postprandial period. l-[ring-2H5]phenylalanine-based MPS increased above basal (0.025 ± 0.008%/h) by ∼75% (0.043 ± 0.009%/h; P = 0.05) between 0 and 120 min and by ∼86% (0.046 ± 0.004%/h; P = 0.02) between 120 and 300 min, respectively. l-[1-13C]leucine-based MPS increased above basal (0.027 ± 0.002%/h) by ∼72% (0.051 ± 0.016%/h; P = 0.10) between 0 and 120 min and by ∼62% (0.047 ± 0.004%/h; P = 0.001) between 120 and 300 min, respectively. Myofibrillar protein-bound l-[1-13C]phenylalanine increased over time (P < 0.001) and equaled 0.004 ± 0.001, 0.008 ± 0.002, 0.017 ± 0.004, and 0.020 ± 0.003 mole percent excess at 60, 120, 180, and 300 min, respectively, of the postprandial period. Milk protein ingestion increased mTORC1 phosphorylation at 120, 180, and 300 min of the postprandial period (all P < 0.05). Our results show that ingestion of 38 g of milk protein results in sustained increases in MPS throughout a 5-h postprandial period in healthy young men

Supplemental Table 1

Feeding and resistance exercise stimulate myofibrillar protein synthesis rates (MPS) in healthy adults. This anabolic characterization of ‘healthy adults’ has been namely focused on males. Therefore, the purpose of this study was to examine the temporal responses of MPS and anabolic signaling to resistance exercise alone or combined with the ingestion of protein in post-menopausal females and compare postabsorptive rates with young females. Sixteen females (60 ± 7 y; BMI = 26 ± 12 kg·m-2) completed an acute bout of unilateral resistance exercise before consuming either: a fortified whey protein supplement (WHEY) or water. Participants received primed continuous infusions of L-[ring-13C6]phenylalanine with bilateral muscle biopsies before and after treatment ingestion at 2 h and 4 h in non-exercised and exercised legs. Resistance exercise transiently increased MPS above baseline at 0-2 h in the water condition (P = 0.007). Feeding after exercise resulted in a late phase (2-4 h) increase in MPS in the WHEY condition (P = 0.005). In both conditions, exercise did not enhance the cumulative (0-4 h) MPS response. In the non-exercised leg, MPS did not differ at 0-2 h, 2-4 h, or 0-4 h of the measurement periods (all, P > 0.05). Likewise, there were no changes in the phosphorylation of p70S6K, AMPKα, or total and phosphorylated yes-associated protein on Ser127. Post-absorptive MPS were lower in pre-menopausal vs. post-menopausal females (P = 0.023). We show that resistance exercise-induced changes in MPS are temporally regulated, but do not result in greater cumulative (0-4 h) MPS in post-menopausal women.</p

Small-Scale Randomized Controlled Trial to Explore the Impact of β-Hydroxy-β-Methylbutyrate Plus Vitamin D₃ on Skeletal Muscle Health in Middle Aged Women

β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D 3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women