Thesis (Ph. D.)--University of Missouri--Columbia, 2002. / "December 2002." Typescript. Vita. Includes bibliographical references (leaves 143-155). Also available on the Internet.

Carbohydrate plus additional protein supplementation provided immediately after exercise has been found to increase the rate of muscle glycogen restoration compared to carbohydrate alone. To examine whether leucine, and/or β-hydroxy-β-methylbutyrate (HMB) to carbohydrate plus protein supplementation affects short-term recovery (45 min) of muscle glycogen, we compared plasma glucose and insulin, the muscle glycogen concentration, and the cellular signaling proteins controlling muscle glycogen synthesis 45 min after supplementation. Rats (n=35) underwent high-intensity resistance exercise followed by supplementation with carbohydrate (CHO: 1.2g/kg body weight), carbohydrate with whey protein (CP: 1.2g CHO + 375mg whey protein/kg body weight), carbohydrate with whey protein plus HMB (CPH: 1.2g CHO + 375mg whey protein + 400mg HMB/kg body weight), carbohydrate with whey protein, HMB plus leucine (CPHL: 1.2g CHO + 375mg whey protein + 400mg HMB + 444mg leucine/kg body weight) or exercise only (CON). Blood samples were collected immediately after exercise and 45 min after supplementations. Muscle samples of plantaris were excised immediately and 45 min post-exercise. Plasma glucose was increased by CHO and CPH supplementation and reduced by CPHL at 45 min post-exercise. Plasma insulin was elevated by CP and CPHL treatments compare to CHO. Muscle glycogen concentration was unaffected by all treatments and did not differ from CON. Phosphorylation of Akt/PKB, GSK3α/β, and GS at 45 min of recovery for all supplements was not significant difference from CON. Phosphorylation of mTOR was significantly increased by CPHL and CP supplementation compared to CON, CHO, and CPH. Phosphorylation of AS160 was markedly reduced by CPH supplementation compared to CON. These results suggest that supplementing with carbohydrate plus protein with or without leucine and its metabolite, HMB, to enhance muscle glycogen replenishment following exercise may not provide an advantage during the early phase of recovery (45 min). Furthermore, there is some indication that HMB may elicit insulin resistance, and this needs further evaluation. / text

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Maintenance of adequate muscle glycogen stores has been shown to be essential for endurance performance. For athletes who train on successive days or twice in the same day it is especially important that feeding strategies result in optimal glycogen resynthesis between workouts. The purpose of this investigation was to determine if prior carbohydrate feedings and the form of the carbohydrate consumed affected subsequent endurance performance. Seven endurance trained male cyclists agreed to participate in this study. Each day of testing consisted of two exercise bouts. The first workout was an anaerobic workout consisting of five one minute efforts at 115% VO2max followed by a sprint ride to exhaustion. Each of the sprints was separated from the next by a four minute rest period. For the final ride, the subjects rode at 115% of VO2max. One hour following the completion of the first workout, the subjects began a feeding regimen in which one of four carbohydrate sources were ingested in an amount calculated to provide 1.5g carbohydrate/kg bodyweight/hr for the next four hours. The trials were grouped by carbohydrate forms, dense chewy solid (Powerbars) (DCS), liquid carbohydrate (Gatorlode) (LCHO), and semi-moist solid (Nabisco Snackwells and Fruit Newtons) (SMS). In addition, a water trial (W) was conducted to serve as a control The second workout occurred six hours after the completion of the anaerobic workout and consisted of a one-hour self-paced performance ride on a cycle ergometer. Performance was measured as work (U) performed during the ride. All carbohydrate forms (824.7±109.6 U) improved performance over water (782.0±121.7 U) (p<0.05). In addition, among the various carbohydrate forms, SMS (843.2±94.4 U) significantly improved performance over LCHO (807.3±141 U) and DCS (805.3±115 U) (p<0.05). Carbohydrate feedings between anaerobic and aerobic workouts in the same day improve performance. Also, the physical form of the carbohydrate influences performance. / School of Physical Education

The present study was designed to evaluate the influence of carbohydrate structure on muscle glycogen resynthesis. Eight college-aged male cyclists performed a depletion exercise protocol to decrease vastus lateralis glycogen concentration. This protocol consisted of 60 min of cycling at 75% V O2max, followed by 6 - one min sprints at 125 % V O2max, with a 1 min rest between each sprint. Following the depletion exercise, the subjects consumed - 3000 kcal over a 12 hour period, which was calculated to meet each subject's estimated daily energy expenditure. The carbohydrate (CHO), fat and protein content represented 65:20:15% of the calories consumed, respectively, and totaled 450 - 550 g of CHO. All of the CHO was derived from 1 of 4 solutions: 1) glucose, 2) maltodextrin (glucose polymer), 3) waxy starch (100% amylopectin), or 4) resistant starch (100% amylose). Muscle biopsies were taken after the depletion exercise protocol and 24 hours after the depletion protocol to determine glycogen concentrations. The postdepletion exercise glycogen concentration was similar in all 4 trials, and averaged 234.7 mmol/kg dry weight (d.w.) muscle. Twenty-four hours after exercise, the increase in muscle glycogen concentration was less in the resistant starch trial (90.8 f 12.8 mmol/kg d.w.) than in the glucose, maltodextrin and waxy starch trials, in which glycogen concentration increased 168.7 mmol/kg d.w. Following the 24 h post-depletion exercise biopsy, each subject performed a 30 min cycling time trial, so that the relationship between muscle glycogen concentration and performance could be examined. There were no differences in work output during the time trial or blood lactate concentration immediately following the time trial in any of the trials. In summary, glycogen resynthesis is attenuated following ingestion of carbohydrate with a high amylose content, relative to amylopectin or glucose; however, short duration performance at intensities < 75% VO2max is unaffected. / School of Physical Education

Access to abstract permanently restricted to Ball State community only / Access to thesis permanently restricted to Ball State community only / Department of Biology

Seizure activity is the primary symptom in a common but very serious neurological disorder known as epilepsy. Brain glycogen is utilized for neuronal function, prompting us to investigate the role of brain glycogen during seizure activity in mouse models. Seizures were induced with Pentylenetetrazole (PTZ) in both wild-type mice and mice lacking brain glycogen (MGSKO/GSL30 mice). A time course of brain glycogen utilization after onset of seizure activity revealed a reduction of brain glycogen in wild-type mice. The glycogen synthase activity ratio increased after onset of seizure activity, while the glycogen phosphorylase activity ratio remained constant. Brain and blood glucose levels increased after seizure onset in wild-type mice. Despite lacking brain glycogen, MGSKO/GSL30 mice exhibited acute seizure activity. No differences were observed in seizure intensity, onset time, and duration between genotypes. These findings suggest that brain glycogen is important, but not required for PTZ-induced acute seizure activity in mice. / Access to thesis permanently restricted to Ball State community only / Department of Biology

There is no abstract available for this dissertation. / Human Performance Laboratory

This study compared the exercise responses of a waxy starch (WS), resistant starch (RS), glucose (GL) and an artificially-sweetened placebo (PL) ingested prior to exercise. Ten college-age, male competitive cyclists completed four experimental protocols consisting of a 30 min isokinetic, self-paced performance ride preceded by 90 min of constant load cycling at 66% VO2max. Thirty min prior to exercise, they ingested 1 g•kg-1 body weight of GL, WS, RS, or PL. A familiarization trial was first conducted to eliminate a potential order effect. An order effect was evidenced by lower (p<0.05) work rates during the performance ride of the first trial (390 ± 26.1 kJ) than the other four trials. No order effect was observed for the remainder of the experimental treatments which were performed in a single-blind, randomized fashion. At rest, GL elicited greater (P<0.05) serum glucose and insulin responses than all other trials. During exercise, however, serum glucose and insulin responses were similar among trials. Blood C-peptide and glucagon responses were also similar among trials. The mean total carbohydrate oxidation rates (CHOox) were higher (p<0.05) during the GL, WS, and RS trials (2.59 ± 0.13, 2.49 ± 0.10, and 2.71 ± 0.15 g•min-1, respectively) compared to PL (2.35 ± 0.12 g•min-1). Subjects were able to complete more work (p<0.05) during the performance ride when they ingested GL (434 ± 25.2 kJ) or WS (428 ± 22.5 kJ) compared to PL (403 ± 35.1 kJ). They also tended to produce more work with RS ingestion (418 ± 31.4 kJ), although this did not reach statistical significance (p<0.09). These results indicate that pre-exercise CHO ingestion in the form of starch or glucose maintained higher rates of total carbohydrate oxidation during exercise and provided an ergogenic benefit during self-paced cycling. / Human Performance Laboratory

Lafora disease (LD) is an adolescent-onset autosomal recessive progressive myoclonus epilepsy. The main clinical symptoms of the disease are worsening seizures, neurodegeneration and usually death within ten years. No therapeutics or interventions exist for this devastating disease. Mutations in two genes, EPM2A (laforin) and EPM2B (malin) are causative of more than 90 percent of LD. The pathognomonic sign of LD is the presence of abnormal glycogen which precipitates and accumulates into starch-like masses called Lafora bodies (LB). There are two main hypotheses of LB formation. Glycogen is synthesized through the combined activities of glycogen synthase (GS) and branching enzyme (BE). One hypothesis is that LB form due to an overactivation of GS, causing a misbalance between synthesis and branching. Here, malin and laforin regulate levels of GS and other protein(s) involved in glycogen synthesis and when missing, result in their overaccumulation and thus overactivation of synthesis in relation to branching. The second hypothesis is based on evidence of increased phosphorylation of glycogen in LB. In this hypothesis, glycogen becomes abnormal because of the hyperphosphorylation, causing it to precipitate. Laforin is a glycogen phosphatase, and removes phosphate from glycogen. When missing, as in LD, glycogen becomes hyperphosphorylated and forms LB. A role for malin is less clear in this hypothesis. In this thesis, I identify and characterize a third gene, PRDM8, causing an early onset form of LD in a large consanguineous family. I show that it both interacts with laforin and malin and results in their relocation to the nucleus. I also characterize a laforin-interacting protein, Epm2aip1, finding an important role for this previously uncharacterized protein in glycogen metabolism. Epm2aip1-/- mice exhibit hepatic insulin resistance, decreased hepatic glycogen synthesis, increased liver fat, and resistance against obesity in adulthood. Epm2aip1 associates with glycogen synthase (GS), and its absence impairs the allosteric activation of GS by glucose-6-phosphate. Finally, I find that genetically removing PTG, an activator of GS, from mice with Lafora disease results in near-complete disappearance of LB, and resolution of the neurodegeneration and myoclonic epilepsy. This work has revealed a gateway to the treatment of this devastating and fatal disease.