Caffeinated nitric oxide-releasing lozenge improves cycling time trial performance.

Boosting nitric oxide production during exercise by various means has been found to improve exercise performance. We investigated the effects of a nitric oxide releasing lozenge with added caffeine (70 mg) on oxygen consumption during steady-state exercise and cycling time trial performance using a double-blinded randomized, crossover experimental design. 15 moderately trained cyclists (7 females and 8 males) were randomly assigned to ingest the caffeinated nitric oxide lozenge or placebo 5 min before exercise. Oxygen consumption and blood lactate were assessed at rest and at 50%, 65% and 75% maximal oxygen consumption. Exercise performance was assessed by time to complete a simulated 20.15 km cycling time-trial course. No significant treatment effects for oxygen consumption or blood lactate at rest or during steady-state exercise were observed. However, time-trial performance was improved by 2.1% (p<0.01) when participants consumed the nitric oxide lozenge (2,424±69 s) compared to placebo (2,476±78 s) and without a significant difference in rating of perceived exertion. These results suggest that acute supplementation with a caffeinated nitric oxide releasing lozenge may be a practical and effective means of improving aerobic exercise performance.

Chromium chloride increases insulin-stimulated glucose uptake in the perfused rat hindlimb.

AIM: To determine the effect of chromium chloride (CrCl3 ) on healthy skeletal muscle glucose uptake in the absence and presence of submaximal insulin using the rat hindlimb perfusion technique. METHODS: Sprague-Dawley rats were randomly assigned to an experimental group: basal (Bas), chromium chloride (Cr), submaximal insulin (sIns) or chromium chloride plus submaximal insulin (Cr-sIns). RESULTS: Insulin significantly increased [H(3)]-2 deoxyglucose (2-DG) uptake in the gastrocnemius muscles. Additionally, Cr-sIns displayed greater rates of 2-DG uptake than sIns (Cr-sIns 6.86 ± 0.74 µmol g h(-1) vs. sIns 4.83 ± 0.42 µmol g h(-1)). There was no difference between Cr and Bas treatment groups. It has been speculated that chromium works to increase glucose uptake by increasing insulin signalling. We found that Akt and AS160 phosphorylation was increased in the sINS treatment group, while chromium treatment had no additional effect on Akt or AS160 phosphorylation in the absence or presence of insulin. Cr-sIns significantly increased plasma membrane GLUT4 concentration above that of sIns (Cr-sIns 72.22 ± 12.7%, sIns 53.4 ± 6.1%), but in the absence of insulin, chromium had no effect. CONCLUSION: Exposure of healthy skeletal muscle to chromium may increase skeletal muscle insulin-stimulated GLUT4 translocation and glucose uptake. However, these effects do not appear to result from enhanced insulin signalling proximal to AS160.

Functional electrical stimulation cycling improves body composition, metabolic and neural factors in persons with spinal cord injury.

Persons with spinal cord injury (SCI) are at a heightened risk of developing type II diabetes and cardiovascular disease. The purpose of this investigation was to conduct an analysis of metabolic, body composition, and neurological factors before and after 10 weeks of functional electrical stimulation (FES) cycling in persons with SCI. Eighteen individuals with SCI received FES cycling 2-3 times per week for 10 weeks. Body composition was analyzed by dual X-ray absorptiometry. The American Spinal Injury Association (ASIA) neurological classification of SCI test battery was used to assess motor and sensory function. An oral glucose tolerance (OGTT) and insulin-response test was performed to assess blood glucose control. Additional metabolic variables including plasma cholesterol (total-C, HDL-C, LDL-C), triglyceride, and inflammatory markers (IL-6, TNF-alpha, and CRP) were also measured. Total FES cycling power and work done increased with training. Lean muscle mass also increased, whereas, bone and adipose mass did not change. The ASIA motor and sensory scores for the lower extremity significantly increased with training. Blood glucose and insulin levels were lower following the OGTT after 10 weeks of training. Triglyceride levels did not change following training. However, levels of IL-6, TNF-alpha, and CRP were all significantly reduced.

Post exercise carbohydrate-protein supplementation: phosphorylation of muscle proteins involved in glycogen synthesis and protein translation.

The enzymes Akt, mTOR, p70(S6K), rpS6, GSK3, and glycogen synthase interact in the control of protein and/or glycogen synthesis in skeletal muscle, and each has been found to respond to exercise and nutrient supplementation. In the present study, we tested the hypothesis that nutrient supplementation post exercise, in the form of a carbohydrate-protein (CHO-PRO) supplement, would alter the phosphorylation state of these enzymes in a manner that should increase muscle protein and glycogen synthesis above that produced by exercise alone. After a 45 min cycling session followed by sprints and again 15 min later, the subjects (n = 8) ingested 400 ml of a CHO-PRO drink (7.8% dextrose and 1.8% protein-electrolyte) or a placebo drink, as assigned using a randomized, counter-balanced design with repeated measures. Biopsies of the vastus lateralis were taken before exercise and at 45 min of recovery. At 45 min after supplementation, CHO-PRO treatment yielded greater phosphorylation of Akt (65%), mTOR (86%), rpS6 (85-fold), and GSK3alpha/beta (57%) than pre-exercise levels (p < 0.05). Although p70(S6k) showed an exercise response after 45 min, there were no differences between treatments. Glycogen synthase (GS) phosphorylation was significantly reduced 45 min after exercise for both treatments, but the reduction in phosphorylation was greatest during the CHO-PRO treatment (3-fold decrease; p < 0.05), indicating greater activation of GS following supplementation. No difference between treatments was detected prior to exercise for any of the enzymes. These results suggest that a post exercise CHO-PRO supplement alters the phosporylation levels of the enzymes tested in a manner that should accelerate muscle glycogen synthesis and protein initiation during recovery from cycling exercise.

Attenuation of insulin resistance by chronic beta2-adrenergic agonist treatment possible muscle specific contributions.

A possible mechanism by which chronic clenbuterol treatment causes multiple physiological changes in skeletal muscle that leads to reduced insulin resistance in the obese Zucker rat (falfa) was investigated. Animals were gavaged with clenbuterol (CB) (0.8 mg x kg(-1) day(-1)), terbutaline (TB) (1.0 mg x kg(-1)day(-1)), or control (CT) vehicle for six weeks. Oral glucose tolerance and insulin responses were markedly improved in CB rats and impaired in TB rats. CB treatment caused a 24-34% gain in muscle mass in all muscle fiber types, and increases in 3-O-methyglucose transport (2-fold) and GLUT4 concentration (57%) in fast twitch glycolytic (FG) muscle. Oxidative capacity was reduced in both FG (47%) and fast twitch oxidative (FO) muscle (30%), but not in slow twitch oxidative (SO) muscle. Null model analysis for receptor occlusion demonstrated that most functional beta-adrenoceptors were lost in FO (82%) and FG (89%) fibers, but not in SO fibers. We propose that hypertrophy is the result of continuous direct activation of beta-adrenoceptors while loss in oxidative capacity may be the result of receptor down regulation. Improvements in insulin resistance may have been due, in part, to both increases in lean body mass and specific adaptations in FG muscle.

Effects of clenbuterol on insulin resistance in conscious obese Zucker rats.

The present study was conducted to determine the effect of chronic administration of the long-acting beta(2)-adrenergic agonist clenbuterol on rats that are genetically prone to insulin resistance and impaired glucose tolerance. Obese Zucker rats (fa/fa) were given 1 mg/kg of clenbuterol by oral intubation daily for 5 wk. Controls received an equivalent volume of water according to the same schedule. At the end of the treatment, rats were catheterized for euglycemic-hyperinsulinemic (15 mU insulin. kg(-1). min(-1)) clamping. Clenbuterol did not change body weight compared with the control group but caused a redistribution of body weight: leg muscle weights increased, and abdominal fat weight decreased. The glucose infusion rate needed to maintain euglycemia and the rate of glucose disappearance were greater in the clenbuterol-treated rats. Furthermore, plasma insulin levels were decreased, and the rate of glucose uptake into hindlimb muscles and abdominal fat was increased in the clenbuterol-treated rats. This increased rate of glucose uptake was accompanied by a parallel increase in the rate of glycogen synthesis. The increase in muscle glucose uptake could not be ascribed to an increase in the glucose transport protein GLUT-4 in clenbuterol-treated rats. We conclude that chronic clenbuterol treatment reduces the insulin resistance of the obese Zucker rat by increasing insulin-stimulated muscle and adipose tissue glucose uptake. The improvements noted may be related to the repartitioning of body weight between tissues.

Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats.

Acute exercise and training increase insulin action in skeletal muscle, but the mechanism responsible for this effect is unknown. Activation of the insulin receptor initiates signaling through both the phosphatidylinositol (PI) 3-kinase and the mitogen-activated protein kinase [MAPK, also referred to as extracellular signal-regulated kinases (ERK1/2)] pathways. Acute exercise has no effect on the PI3-kinase pathway signaling elements but does activate the MAPK pathway, which may play a role in the adaptation of muscle to exercise. It is unknown whether training produces a chronic effect on basal activity or insulin response of the MAPK pathway. The present study was undertaken to determine whether exercise training improves the activity of the MAPK pathway or its response to insulin in obese Zucker rats, a well-characterized model of insulin resistance. To accomplish this, obese Zucker rats were studied by using the hindlimb perfusion method with or without 7 wk of treadmill training. Activation of the MAPK pathway was determined in gastrocnemius muscles exposed in situ to insulin. Compared with lean Zucker rats, untrained obese Zucker rats had reduced basal and insulin-stimulated activities of ERK2 and its downstream target p90 ribosomal S6 kinase (RSK2). Seven weeks of training significantly increased basal and insulin-stimulated ERK2 and RSK2 activities, as well as insulin stimulation of MAPK kinase activity. This effect was maintained for at least 96 h in the case of ERK2. The training-induced increase in basal ERK2 activity was correlated with the increase in citrate synthase activity. Therefore, 7 wk of training increases basal and insulin-stimulated ERK2 activity. The increase in basal ERK2 activity may be related to the response of muscle to training.

Dietary strategies to promote glycogen synthesis after exercise.

Muscle glycogen is an essential fuel for prolonged intense exercise, and therefore it is important that the glycogen stores be copious for competition and strenuous training regimens. While early research focused on means of increasing the muscle glycogen stores in preparation for competition and its day-to-day replenishment, recent research has focused on the most effective means of promoting its replenishment during the early hours of recovery. It has been observed that muscle glycogen synthesis is twice as rapid if carbohydrate is consumed immediately after exercise as opposed to waiting several hours, and that a rapid rate of synthesis can be maintained if carbohydrate is consumed on a regular basis. For example, supplementing at 30-min intervals at a rate of 1.2 to 1.5 g CHO x kg(-1) body wt x h(-1) appears to maximize synthesis for a period of 4- to 5-h post exercise. If a lighter carbohydrate supplement is desired, however, glycogen synthesis can be enhanced with the addition of protein and certain amino acids. Furthermore, the combination of carbohydrate and protein has the added benefit of stimulating amino acid transport, protein synthesis and muscle tissue repair. Research suggests that aerobic performance following recovery is related to the degree of muscle glycogen replenishment.

Effect of carbohydrate supplementation on postexercise GLUT-4 protein expression in skeletal muscle.

The effect of carbohydrate supplementation on skeletal muscle glucose transporter GLUT-4 protein expression was studied in fast-twitch red and white gastrocnemius muscle of Sprague-Dawley rats before and after glycogen depletion by swimming. Exercise significantly reduced fast-twitch red muscle glycogen by 50%. During a 16-h exercise recovery period, muscle glycogen returned to control levels (25.0 +/- 1.4 micromol/g) in exercise-fasted rats (24.2 +/- 0. 3 micro). However, when carbohydrate supplementation was provided during and immediately postexercise by intubation, muscle glycogen increased 77% above control (44.4 +/- 2.1 micromol/g). Exercise-fasting resulted in an 80% increase in fast-twitch red muscle GLUT-4 mRNA but only a 43% increase in GLUT-4 protein concentration. Conversely, exercise plus carbohydrate supplementation elevated fast-twitch red muscle GLUT-4 protein concentration by 88% above control, whereas GLUT-4 mRNA was increased by only 40%. Neither a 16-h fast nor carbohydrate supplementation had an effect on fast-twitch red muscle GLUT-4 protein concentration or on GLUT-4 mRNA in sedentary rats, although carbohydrate supplementation increased muscle glycogen concentration by 40% (35.0 +/- 0.9 micromol/g). GLUT-4 protein in fast-twitch white muscle followed a pattern similar to fast-twitch red muscle. These results indicate that carbohydrate supplementation, provided with exercise, will enhance GLUT-4 protein expression by increasing translational efficiency. Conversely, postexercise fasting appears to upregulate GLUT-4 mRNA, possibly to amplify GLUT-4 protein expression on an increase in glucose availability. These regulatory mechanisms may help control muscle glucose uptake in accordance with glucose availability and protect against postexercise hypoglycemia.

The effect of a carbohydrate--arginine supplement on postexercise carbohydrate metabolism.

The effect of a carbohydrate-arginine supplement on postexercise muscle glycogen storage was investigated. Twelve well-trained cyclists rode for 2 hr on two separate occasions to deplete their muscle glycogen stores. At 0, 1, 2, and 3 hr after each exercise bout, the subjects ingested either a carbohydrate (CHO) supplement (1 g carbohydrate/kg body weight) or a carbohydrate-arginine (CHO/AA) supplement (1 g carbohydrate/kg body mass and 0.08 g arginine-hydrochloride/kg body weight). No difference in rate of glycogen storage was found between the CHO/AA and CHO treatments, although significance was approached. There were also no differences in plasma glucose, insulin, or blood lactate responses between treatments. Postexercise carbohydrate oxidation during the CHO/AA treatment was significantly reduced compared to the CHO treatment. These results suggest that the addition of arginine to a CHO supplement reduces the rate of CHO oxidation postexercise and therefore may increase the availability of glucose for muscle glycogen storage during recovery.

Role of carbohydrate in physical activity.

Carbohydrate is an essential fuel for prolonged, strenuous exercise, although the carbohydrate stores of the body are limited. Research studies have provided evidence that carbohydrate depletion is associated with fatigue, decrease in exercise intensity, and even exercise cessation. With the appropriate diet and exercise protocol, however, the carbohydrate stores of the body can be substantially increased and exercise performance improved by carbohydrate supplementation before and during exercise. In this article, the role of carbohydrate supplementation for increasing carbohydrate stores before exercise, maintaining blood glucose during exercise, and the rapid replenishment of the carbohydrate stores after exercise are discussed. Considered in the discussion are the types, amounts and forms of carbohydrate supplements that are most effective, and the most appropriate times for their ingestion.

Attenuating the decline in ATP arrests the exercise training-induced increases in muscle GLUT4 protein and citrate synthase activity.

Thirty-two female Sprague-Dawley rats were assigned to one of four groups: control (CON); exercise training (TR); exercise training + clenbuterol treatment (0.8 mg kg body wt(-1) d(-1)) (TR + CL) or exercise training + clenbuterol treatment + 2% beta-guanidinoproprionic acid diet (TR + CL + beta) to examine whether alterations in the high energy phosphate state of the muscle mediates exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity. Exercise training consisted of running the rats 5 d week(-1) for 8 weeks on a motor-driven treadmill (32 m min(-1), 15% grade). Gastrocnemius GLUT4 protein concentration and citrate synthase activity were significantly elevated in the TR animals, but these adaptations were attenuated in the TR + CL animals. Providing beta-GPA in combination with clenbuterol enabled training to elevate GLUT4 protein concentration and citrate synthase activity, with the increase in GLUT4 being greater than that observed for the TR animals. Skeletal muscle ATP levels were reduced in the TR + CL + beta animals while ATP levels in the TR + CL animals were significantly elevated compared with CON. An acute 40-min bout of electrical stimulation of the sciatic nerve was found to lower skeletal muscle ATP levels by approximately 50% and elevate cAMP levels in all groups. No difference in post-contraction cAMP levels were observed among groups. However, post-contraction ATP levels in the TR + CL animals were significantly greater than the other groups. Collectively, these findings suggest that exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity are initiated in response to a reduction in the skeletal muscle ATP concentration.

Regulation of GLUT4 protein expression and glycogen storage after prolonged exercise.

The purpose of this study was to determine the time course of GLUT4 protein accumulation following an exercise-carbohydrate supplementation regimen, and to evaluate the effect of this regimen on GLUT4 mRNA regulation. Rats were exercised by swimming and intubated with 1 mL of a 50% glucose solution immediately post-exercise. Exercise significantly reduced muscle glycogen by 50%. By 1.5 h of recovery, muscle glycogen was normalized, but continued to increase above the control level during the next 16 h. A faster and larger repletion of glycogen occurred in the fast-twitch red compared with the fast-twitch white muscle during the 16 h of recovery. GLUT4 protein concentration in fast-twitch red muscle was significantly increased above control by 1.5 h of recovery, and progressively increased throughout the recovery period. Fast-twitch white muscle demonstrated a similar trend, but the increase in GLUT4 protein did not reach significance until 5 h of recovery. Fast-twitch red muscle GLUT4 mRNA was increased by 53% above control immediately post-exercise, but returned to the control level by 1.5 h of recovery. GLUT4 mRNA associated with polysomes, however, increased significantly during this time and remained elevated for a minimum of 5 h. The results suggest that the increased GLUT4 protein expression following a regimen of exercise-carbohydrate supplementation occurs sufficiently fast to contribute to the resynthesis of muscle glycogen, and is controlled by both pre-translational and translational mechanisms.

Increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals.

We have recently demonstrated that insulin activates farnesyltransferase (FTase) and thereby increases the amounts of cellular farnesylated p21Ras in 3T3-L1 fibroblasts, adipocytes and vascular smooth muscle cells. We postulated that hyperinsulinaemia might considerably increase the the cellular pool of farnesylated p21Ras available for activation by other growth factors. To examine the role of in vivo hyperinsulinaemia in regulating farnesylated p21Ras, we measured the amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals. Liver, aorta, and skeletal muscle of ob/ob mice, and mice made obese and hyperinsulinaemic by injection of gold-thioglucose contained greater amounts of farnesylated p21Ras than tissues of their lean normoinsulinaemic counterparts. Similarly, farnesylated p21Ras was increased (67 vs. 35 % in control animals, p<0.01) in the livers of hyperinsulinaemic Zucker rats (fa/fa). Reduction of hyperinsulinaemia by exercise training (2 h/day for 7-8 weeks) resulted in decreases in the amounts of farnesylated p21Ras in these animals. Increased farnesylated p21Ras in hyperinsulinaemic animals reflected increasing increments in the activity of FTase in ob/ob mice (2-fold increase) and fa/fa Zucker rats (3.5-fold increase), while the total amounts of Ras proteins remained unchanged. In contrast to insulin-resistant hyperinsulinaemic animals, denervated insulin-resistant rat soleus muscle (in the presence of normoinsulinaemia) showed normal amounts of farnesylated p21Ras. In summary, these data confirm increased amounts of farnesylated p21Ras in tissues of hyperinsulinaemic animals.

Prevention and treatment of non-insulin-dependent diabetes mellitus.

The benefits of exercise training in the prevention and treatment of insulin resistance, impaired glucose homeostasis, and NIDDM are strongly supported by current research. The actual mechanisms involved have not been completely identified but occur at the systemic, tissue, and cellular levels. The adaptations that are responsible for the prophylactic effects of exercise training, however, start to subside rapidly once training ceases and are completely lost within 1 to 2 weeks of detraining [4, 17, 37, 68, 161]. Thus, the benefits of exercise training must be renewed on a regular basis. In addition, many of the systemic and cellular adaptations that are responsible for an improved skeletal muscle insulin action occur in only those muscles involved in the training program [4, 28]. Therefore, exercise training programs that consist of various modes of exercise, and which require the use of a large muscle mass, such as swimming, power walking, and strength training, may be the most advantageous for the prevention and treatment of insulin resistance and associated diseases.

Amylin-mediated inhibition of insulin-stimulated glucose transport in skeletal muscle.

We examined the effects of amylin on 3-O-methyl-D-glucose (3-O-MG) transport in perfused rat hindlimb muscle under hyperinsulinemic (350 microU/ml, 2,100 pmol/l) conditions. Amylin at 100 nmol/l concentration inhibited 3-O-MG transport relative to control in all three basic muscle fiber types. Transport decreased in slow-twitch oxidative (from 5.65 +/- 1.13 to 3.46 +/- 0.71 micromol . g-1 . h-1), fast-twitch oxidative (from 6.84 +/- 0.90 to 4.84 +/- 0.76 micromol . g-1 . h-1), and fast-twitch glycolytic (from 1.27 +/- 0.20 to 0.60 +/- 0.05 micromol . g-1 . h-1) muscle. Amylin inhibition of insulin-stimulated glucose transport in skeletal muscle was accompanied by a 433 +/- 72% increase in intracellular glucose 6-phosphate (G-6-P) despite the absence of extracellular glucose. The source of hexose units for the formation and maintenance of G-6-P was likely glycogen. Amylin increased glycogenolysis, increased lactate formation, and decreased glycogen synthase activity. Furthermore, the kinetics of glycogen synthase suggest that this enzyme may control intracellular G-6-P concentration. Despite the large increase in G-6-P, no detectable increase in uridine diphosphate-N-acetylhexosamines occurred, suggesting that the proposed glucosamine pathway may not be involved in transport inhibition. However, decreases in uridine diphosphate hexoses were detected. Therefore, uridine or hexosamine-based metabolites may be involved in amylin action.

Glycogen resynthesis after exercise: effect of carbohydrate intake.

To maximize glycogen resynthesis after exercise, a carbohydrate supplement in excess of 1.0 g x kg(-1) body wt should be consumed immediately after competition or a training bout. Continuation of supplementation every two hours will maintain a rapid rate of storage up to six hours post exercise. Supplements composed of glucose or glucose polymers are the most effective for replenishment of muscle glycogen, whereas fructose is most beneficial for the replenishment of liver glycogen. The addition of protein to a carbohydrate supplement may also increase the rate of glycogen storage due to the ability of protein and carbohydrate to act synergistically on insulin secretion.

Effect of chronic electrical stimulation and beta-GPA diet on GLUT4 protein concentration in rat skeletal muscle.

The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.

Effect of pyruvate and dihydroxyacetone on metabolism and aerobic endurance capacity.

Pyruvate and dihydroxyacetone are three carbon compounds that when infused directly into the blood or taken orally produce strong metabolic effects. When chronically fed to animals as part of their diet, pyruvate plus dihydroxyacetone reduce the rate of weight gain and body fat content during growth. These alterations in growth pattern appear to be the result of an increased loss of calories as heat at the expense of storage of lipid. Pyruvate-dihydroxyacetone supplementation has also been found to improve the insulin sensitivity of insulin resistant rats and reduce plasma cholesterol levels induced by a high cholesterol diet as well as lower blood pressure and heart rate in obese individuals. When infused in rats during prolonged treadmill running, pyruvate reduced run time to exhaustion by approximately 67%. However, when provided as an oral supplement for several days, it has enhanced aerobic endurance capacity. The mechanism of action is unclear, but available data suggest that the increase in performance following pyruvate-dihydroxyacetone supplementation may be a result of an increased reliance on blood glucose, thus sparing muscle glycogen. In summary, chronic supplementation of pyruvate-dihydroxyacetone may be beneficial from a preventive medicine prospective as well as for certain athletic endeavors.

Regulation of GLUT4 protein and glycogen synthase during muscle glycogen synthesis after exercise.

The pattern of muscle glycogen synthesis following its depletion by exercise is biphasic. Initially, there is a rapid, insulin independent increase in the muscle glycogen stores. This is then followed by a slower insulin dependent rate of synthesis. Contributing to the rapid phase of glycogen synthesis is an increase in muscle cell membrane permeability to glucose, which serves to increase the intracellular concentration of glucose-6-phosphate (G6P) and activate glycogen synthase. Stimulation of glucose transport by muscle contraction as well as insulin is largely mediated by translocation of the glucose transporter isoform GLUT4 from intracellular sites to the plasma membrane. Thus, the increase in membrane permeability to glucose following exercise most likely reflects an increase in GLUT4 protein associated with the plasma membrane. This insulin-like effect on muscle glucose transport induced by muscle contraction, however, reverses rapidly after exercise is stopped. As this direct effect on transport is lost, it is replaced by a marked increase in the sensitivity of muscle glucose transport and glycogen synthesis to insulin. Thus, the second phase of glycogen synthesis appears to be related to an increased muscle insulin sensitivity. Although the cellular modifications responsible for the increase in insulin sensitivity are unknown, it apparently helps maintain an increased number of GLUT4 transporters associated with the plasma membrane once the contraction-stimulated effect on translocation has reversed. It is also possible that an increase in GLUT4 protein expression plays a role during the insulin dependent phase.