scholarly journals Pharmacological Vasodilation Improves Insulin-Stimulated Muscle Protein Anabolism but Not Glucose Utilization in Older Adults

Diabetes ◽  
2010 ◽  
Vol 59 (11) ◽  
pp. 2764-2771 ◽  
Author(s):  
K. L. Timmerman ◽  
J. L. Lee ◽  
S. Fujita ◽  
S. Dhanani ◽  
H. C. Dreyer ◽  
...  
2015 ◽  
Vol 173 (1) ◽  
pp. R25-R34 ◽  
Author(s):  
Jorn Trommelen ◽  
Bart B L Groen ◽  
Henrike M Hamer ◽  
Lisette C P G M de Groot ◽  
Luc J C van Loon

BackgroundThough it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis ratesin vivoin humans.ObjectiveTo assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults.DesignA systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects.ConclusionsFrom the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.


2018 ◽  
Vol 74 (10) ◽  
pp. 1598-1604 ◽  
Author(s):  
Melissa M Markofski ◽  
Kristofer Jennings ◽  
Kyle L Timmerman ◽  
Jared M Dickinson ◽  
Christopher S Fry ◽  
...  

Abstract Background Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. Objective In this Phase 1, double-blind, placebo-controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. Methods We phone-screened 971, enrolled 109, and randomized 50 independent, low-active, nonfrail, and nondiabetic older adults (age 72 ± 1 years). We used a 2 × 2 factorial design. The interventions were: daily nutritional supplementation (15 g EAA or placebo) and physical activity (supervised AE training 3 days/week or monitored habitual activity) for 24 weeks. Muscle strength, physical function, body composition, and muscle protein synthesis were measured before and after the 24-week intervention. Results Forty-five subjects completed the 24-week intervention. VO2peak and walking speed increased (p < .05) in both AE groups, irrespective of supplementation type, but muscle strength increased only in the EAA + AE group (p < .05). EAA supplementation acutely increased (p < .05) muscle protein synthesis from basal both before and after the intervention, with a larger increase in the EAA + AE group after the intervention. Total and regional lean body mass did not change significantly with any intervention. Conclusions In nonfrail, independent, healthy older adults AE training increased walking speed and aerobic fitness, and, when combined with EAA supplementation, it also increased muscle strength and EAA-stimulated muscle protein synthesis. These increases occurred without improvements in muscle mass.


2012 ◽  
Vol 303 (4) ◽  
pp. R376-R386 ◽  
Author(s):  
Ashley N. Bailey ◽  
Austin D. Hocker ◽  
Benjamin R. Vermillion ◽  
Keith Smolkowski ◽  
Steven N. Shah ◽  
...  

Total knee arthroplasty (TKA) is the most common and a cost-effective surgical remediation for older adults with long-standing osteoarthritis. In parallel with the expanding population of older adults, the number of TKAs performed annually is projected to be 3.48 million by 2030. During this surgery, a tourniquet is used to stop blood flow to the operative leg. However, the molecular pathways that are affected by tourniquet use during TKA continue to be elucidated. We hypothesized that components of the catabolic FoxO3a (i.e., MuRF1, MAFbx, and Bnip3) pathway, as well as the cellular stress pathways [i.e., stress-activated protein kinase (SAPK)/JNK and MAPKs], are upregulated during TKA. The purpose of this study was to measure changes in transcripts and proteins involved in muscle cell catabolic and stress-activated pathways. We obtained muscle biopsies from subjects, 70 ± 1.3 yr, during TKA, from the vastus lateralis at baseline (before tourniquet inflation), during maximal ischemia (just before tourniquet release), and during reperfusion. Total tourniquet time was 43 ± 2 min and reperfusion time was 16 ± 1. Significant increases in FoxO3a downstream targets, MAFbx and MuRF1, were present for mRNA levels during ischemia (MAFbx, P = 0.04; MuRF1, P = 0.04), and protein expression during ischemia (MAFbx, P = 0.002; MuRF1, P = 0.001) and reperfusion (MuRF1, P = 0.002). Additionally, stress-activated JNK gene expression ( P = 0.01) and protein were elevated during ischemia ( P = 0.001). The results of this study support our hypothesis that protein degradation pathways are stimulated during TKA. Muscle protein catabolism is likely to play a role in the rapid loss of muscle volume measured within 2 wk of this surgery.


Geriatrics ◽  
2020 ◽  
Vol 5 (1) ◽  
pp. 6 ◽  
Author(s):  
Susan Morris ◽  
James D. Cater ◽  
Mark A. Green ◽  
Alexandra M. Johnstone ◽  
Jeffrey M. Brunstrom ◽  
...  

The current dietary recommendation for protein intake in the UK is 0.75 g/kg/day, however, this population-wide recommendation does not necessarily reflect altered requirements for older adults to maintain muscle protein synthesis, nor does it encompass the potential impact of intake timing. Optimal muscle protein synthesis in older adults requires both higher intake requirements and a distribution of protein intake above a 25 g threshold, three times across the day. This study aimed to describe the protein intake of older adults in a UK region and compare the results to recommendations. The study re-assessed two existing datasets with rich diet information for older adults in the South Yorkshire area. Data were extracted from food diaries of 256 adults aged between 65 and 89 years old (mean ± SD 72.4 ± 5.3 years). Quantity and timing of intake were coded using Nutritics software and compared to recommendations. The relationship between body mass index (BMI), age, and protein intake was explored. Fewer than 50% of the participants met current UK recommendations (0.75 g/kg/day) and fewer than 15% met the ESPEN 1.2 g/kg/day age-specific recommendation. Only one participant met the 25 g/meal recommendation across three meals. These findings suggest that the older adult population is not achieving recommendations to maintain muscle protein synthesis. Nonetheless it identifies several straightforward opportunities for improvement, notably elevation of morning intake.


Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2285 ◽  
Author(s):  
Konstantinos Prokopidis ◽  
Mavil May Cervo ◽  
Anoohya Gandham ◽  
David Scott

The continuous population increase of older adults with metabolic diseases may contribute to increased prevalence of sarcopenia and obesity and requires advocacy of optimal nutrition treatments to combat their deleterious outcomes. Sarcopenic obesity, characterized by age-induced skeletal-muscle atrophy and increased adiposity, may accelerate functional decline and increase the risk of disability and mortality. In this review, we explore the influence of dietary protein on the gut microbiome and its impact on sarcopenia and obesity. Given the associations between red meat proteins and altered gut microbiota, a combination of plant and animal-based proteins are deemed favorable for gut microbiota eubiosis and muscle-protein synthesis. Additionally, high-protein diets with elevated essential amino-acid concentrations, alongside increased dietary fiber intake, may promote gut microbiota eubiosis, given the metabolic effects derived from short-chain fatty-acid and branched-chain fatty-acid production. In conclusion, a greater abundance of specific gut bacteria associated with increased satiation, protein synthesis, and overall metabolic health may be driven by protein and fiber consumption. This could counteract the development of sarcopenia and obesity and, therefore, represent a novel approach for dietary recommendations based on the gut microbiota profile. However, more human trials utilizing advanced metabolomic techniques to investigate the microbiome and its relationship with macronutrient intake, especially protein, are warranted.


2020 ◽  
Vol 150 (9) ◽  
pp. 2322-2335
Author(s):  
Ling-Yu Li ◽  
Jia-Min Li ◽  
Li-Jun Ning ◽  
Dong-Liang Lu ◽  
Yuan Luo ◽  
...  

ABSTRACT Background Fish cannot use carbohydrate efficiently and instead utilize protein for energy supply, thus limiting dietary protein storage. Protein deposition is dependent on protein turnover balance, which correlates tightly with cellular energy homeostasis. Mitochondrial fatty acid β-oxidation (FAO) plays a crucial role in energy metabolism. However, the effect of remodeled energy homeostasis caused by inhibited mitochondrial FAO on protein deposition in fish has not been intensively studied. Objectives This study aimed to identify the regulatory role of mitochondrial FAO in energy homeostasis maintenance and protein deposition by studying lipid, glucose, and protein metabolism in fish. Methods Carnitine-depleted male Nile tilapia (initial weight: 4.29 ± 0.12 g; 3 mo old) were established by feeding them with mildronate diets (1000 mg/kg/d) for 6 wk. Zebrafish deficient in the carnitine palmitoyltransferase 1b gene (cpt1b) were produced by using CRISPR/Cas9 gene-editing technology, and their males (154 ± 3.52 mg; 3 mo old) were used for experiments. Normal Nile tilapia and wildtype zebrafish were used as controls. We assessed nutrient metabolism and energy homeostasis–related biochemical and molecular parameters, and performed 14C-labeled nutrient tracking and transcriptomic analyses. Results The mitochondrial FAO decreased by 33.1–88.9% (liver) and 55.6–68.8% (muscle) in carnitine-depleted Nile tilapia and cpt1b-deficient zebrafish compared with their controls (P &lt; 0.05). Notably, glucose oxidation and muscle protein deposition increased by 20.5–24.4% and 6.40–8.54%, respectively, in the 2 fish models compared with their corresponding controls (P &lt; 0.05). Accordingly, the adenosine 5′-monophosphate–activated protein kinase/protein kinase B–mechanistic target of rapamycin (AMPK/AKT-mTOR) signaling was significantly activated in the 2 fish models with inhibited mitochondrial FAO (P &lt; 0.05). Conclusions These data show that inhibited mitochondrial FAO in fish induces energy homeostasis remodeling and enhances glucose utilization and protein deposition. Therefore, fish with inhibited mitochondrial FAO could have high potential to utilize carbohydrate. Our results demonstrate a potentially new approach for increasing protein deposition through energy homeostasis regulation in cultured animals.


2010 ◽  
Vol 42 ◽  
pp. 75-76
Author(s):  
Charles Paul Lambert ◽  
B. Selma Mohammed ◽  
Dennis T. Villareal ◽  
Linda R. Peterson ◽  
Brian N. Finck ◽  
...  

2011 ◽  
Vol 300 (3) ◽  
pp. R655-R662 ◽  
Author(s):  
Todd A. Trappe ◽  
Chad C. Carroll ◽  
Jared M. Dickinson ◽  
Jennifer K. LeMoine ◽  
Jacob M. Haus ◽  
...  

Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 ± 2 yr; n = 12), acetaminophen (64 ± 1 yr; n = 11; 4 g/day), and ibuprofen (64 ± 1 yr; n = 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar ( P > 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 ± 14 cm3, 12.5%; ibuprofen: 84 ± 10 cm3, 10.9%) and muscle strength (acetaminophen: 19 ± 2 kg; ibuprofen: 19 ± 2 kg) to a greater extent ( P < 0.05) than placebo (muscle volume: 69 ± 12 cm3, 8.6%; muscle strength: 15 ± 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced ( P > 0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced ( P > 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 ± 8%; P < 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles ( P > 0.05). Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.


2020 ◽  
pp. 1-11 ◽  
Author(s):  
Eunice T. Olaniyan ◽  
Fiona O’Halloran ◽  
Aoife L. McCarthy

Abstract Amino acid bioavailability is critical for muscle protein synthesis (MPS) and preservation of skeletal muscle mass (SMM). Ageing is associated with reduced responsiveness of MPS to essential amino acids (EAA). Further, the older adult population experiences anabolic resistance, leading to increased frailty, functional decline and depleted muscle mass preservation, which facilitates the need for increased protein intake to increase their SMM. This review focuses on the role of proteins in muscle mass preservation and examines the contribution of EAA and protein intake patterns to MPS. Leucine is the most widely studied amino acid for its role as a potent stimulator of MPS, though due to inadequate data little is yet known about the role of other EAA. Reaching a conclusion on the best pattern of protein intake has proven difficult due to conflicting studies. A mixture of animal and plant proteins can contribute to increased MPS and potentially attenuate muscle wasting conditions; however, there is limited research on the biological impact of protein blends in older adults. While there is some evidence to suggest that liquid protein foods with higher than the RDA of protein may be the best strategy for achieving high MPS rates in older adults, clinical trials are warranted to confirm an association between food form and SMM preservation. Further research is warranted before adequate recommendations and strategies for optimising SMM in the elderly population can be proposed.


Sign in / Sign up

Export Citation Format

Share Document