The <i>phka</i>1 deficient I/LnJ mouse exhibits endurance exercise deficiency with no compensatory changes in glycolytic gene expression

Abstract

During exercise, phosphorylase kinase (PhK) is the key regulatory enzyme responsible for maintaining glycogenolytic flux to sustain muscle contraction. The absence of PhK in skeletal muscle results in glycogen storage disease (GSD) Type IX which is characterized by muscle weakness and rapid fatigue upon exercise. In this study, we have used the phka1 deficient I/LnJ mouse model of GSD to investigate the physiological and genetic adaptations that occur in response to voluntary exercise. When quantified over training periods of either 1, 2, or 5 weeks, I/LnJ mice ran significantly less time/day and distance/day than agematched C57/Bl6 mice. Cumulatively after five weeks, adult I/LnJ mice ran ~1/2 the total time and distance of wild-type mice, 116 ± 6 hours and 211 ± 23 km versus 194 ± 3 hours and 418 ± 4 km, respectively. After 5 weeks, C57/Bl6 mice demonstrated an increase in endurance as a result of aerobic training; this observed physiological adaptation was not present in I/LnJ mice. The decrease in total distance run by I/LnJ mice was not due to a reduction in speed; juvenile and adult I/LnJ mice ran ~75%-80% as fast as C57/Bl6 mice. When transcription of glycolytic genes glucose transporter 4 (scla1), pyruvate dehydrogenase (pdha1), and phosphofructokinase (pfk) were quantified at the end of each training period, no significant differences in expression levels were found between mouse strains, suggesting that non-glycolytic mechanisms work to maintain the muscle function observed in the I/LnJ mice.

Expanding the clinicopathological-genetic spectrum of glycogen storage disease type IXd by a Chinese neuromuscular center

“…In vivo , the phka1 -deficient I-strain mouse exhibited almost no expression of Phka1 , resulting in loss of the ability to associate with the other Phk subunits to form the holoenzyme complex ( 32 ). Another phka1 -deficient I/LnJ mouse exhibited half-decreased running time and distance compared to wild-type mice ( 33 ). However, the transcriptional expression of key enzymes necessary for glucose transport and glycolytic flux was not significantly different between phka1 -deficient I/LnJ mice and wild-type mice, suggesting that non-glycolytic mechanisms work to maintain muscle function in phka1 -deficient I/LnJ mice ( 33 ).…”

Test-Retest Reliability and the Learning Effect on Isokinetic Fatigue in Female Master’s Cyclists

“…In order to determine the learning effect associated with isokinetic exercise, the baseline evaluation was considered trial 1, and no familiarization was provided to the equipment or protocol. Participants were also not permitted to be in the laboratory while other evaluations were being conducted in order to ensure initial introduction to the assessment was standardized (Brown & Weir, 2001). None of the participants had ever undergone isokinetic exercise testing prior to participating in this investigation.…”

“…Isokinetic exercise is commonly used as a benchmark for establishing baseline strength values and tracking longitudinal performance gains (Lund, Sondergaard, Zachariasssen, Christensen, Bulow, & Henriksen, 2005). To establish trustworthy isokinetic exercise results, reliable measurement techniques are required with regard to specific devices, procedures, and participant positioning (Brown, & Weir, 2001;Caruso, Brown & Tufano, 2012). Initial studies involving isokinetic exercise have established strong test-retest reliability for devices such as the Cybex, KinCom, and Biodex dynamometers (Alvares, Rodrigues, Azevedo Franke, da Silva, Pinto, & Vaz, 2015;Gross, Huffman, Phillips, & Wray, 1991;Kramer, 1990;Tsiros, Grimshaw, Shield, & Buckley, 2011).…”