Effects of physical activity levels and nutritional intake on skeletal muscle protein turnover and cellular signaling

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Title: Effects of physical activity levels and nutritional intake on skeletal muscle protein turnover and cellular signaling
Author: Erin Leigh Glynn
Abstract: Loss of muscle mass is common in many clinical conditions such as cancer , AIDS , burns and paralysis as well as in aging . Decreased muscle mass can contribute to many other complications and co -morbidities related to diseases , trauma and aging including overall weakness , immobility , increased risk of falls , impaired stress response and metabolic dysfunction . Nutrition and resistance exercise are two readily available and extremely anabolic stimuli for skeletal muscle , though their specific cellular mechanisms remain largely unknown . Studies were designed to examine the mammalian target of rapamycin (mTOR ) muscle hypertrophy pathway in conditions of differing physical activity levels , to determine the effects of low and high carbohydrate and insulin levels (combined with essential amino acids ) on protein turnover and cellular signaling following resistance exercise , and to investigate similar parameters in response to various combinations of anabolic nutrients . Stable isotopic techniques with arterial /venous catheterization and muscle biopsies , immunoprecipitation and immunoblotting , quantitative real -time PCR and hormone (ELISA ) assays were utilized to examine muscle protein turnover , cellular signaling pathways , mRNA expression related to proteins of interest and hormonal responses , respectively . The main findings from these studies were that increased physical activity downregulated the mTOR signaling pathway and decreased inhibitory phosphorylation of insulin receptor substrate 1 (IRS -1 ) . In contrast , mTOR activity may play an important role in paraplegia -induced muscle atrophy as 10 weeks of paraplegia in rats significantly downregulated the mTOR pathway . In humans and compared to modest carbohydrate ingestion , higher amounts of carbohydrate and consequent increases in circulating insulin were unable to further reduce muscle protein breakdown , associated signaling or mRNA expression following a bout of resistance exercise . Similarly , increasing concentrations of leucine may not provide any additional benefit to net protein balance , as has been previously proposed . These studies further our understanding of muscle hypertrophy and atrophy , and begin to provide the scientific data necessary in order to establish evidence -based recommendations for the maintenance of skeletal muscle mass during conditions of muscle wasting .
URI: http : / /hdl .handle .net /2152 .3 /84
Date: 2010-03-03

Citation

Effects of physical activity levels and nutritional intake on skeletal muscle protein turnover and cellular signaling. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /84 .

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