Rate Of Glycogen Synthesis Research Articles

The control of hepatic glycogen metabolism in an in vitro model of sepsis

Culturing hepatocytes with a combination of LPS, TNF-alpha, IL-1beta and IFN-gamma resulted in an inhibition of glucose output from glycogen and prevented the repletion of glycogen in freshly cultured cells. The reduced glycogen mobilisation correlated with the lower cell glycogen content and reduced rate of glycogen synthesis from [U-(14)C]glucose rather than alterations in either total phosphorylase or phosphorylase a activity. There was no change in the percentage of glycogen exported as glucose nor the production of lactate plus pyruvate indicating that redistribution of the Gluc-6-P cannot explain the failure of the liver to export glucose. Although changes in glycogen mobilisation correlated with NO production, inhibition of NO synthase by inclusion of L-NMMA in the culture medium failed to prevent the inhibition of either glycogen accumulation or mobilisation by the proinflammatory cytokines, precluding the involvement of NO in this response. LPS plus cytokine treatment had no effect on total glycogen synthase activity although the activity ratio was lowered, indicative of increased phosphorylation. The inhibition of glycogen synthesis correlated with a fall in the intracellular concentrations of Gluc-6-P and UDP-glucose and in the absence of measured changes in kinase activity, it is suggested that the fall in Gluc-6-P reduces both substrate supply and glycogen synthase phosphatase activity. The fall in Gluc-6-P coincided with a reduction in total glucokinase and hexokinase activity within the cells, but no significant change in either the translocation of glucokinase or glucose-6-phosphatase activity. This demonstrates direct cytokine effects on glycogen metabolism independent of changes in glucoregulatory hormones.

Glucose infusion causes insulin resistance in skeletal muscle of rats without changes in Akt and AS160 phosphorylation

Hyperglycemia is a defining feature of Type 1 and 2 diabetes. Hyperglycemia also causes insulin resistance, and our group (Kraegen EW, Saha AK, Preston E, Wilks D, Hoy AJ, Cooney GJ, Ruderman NB. Am J Physiol Endocrinol Metab Endocrinol Metab 290: E471-E479, 2006) has recently demonstrated that hyperglycemia generated by glucose infusion results in insulin resistance after 5 h but not after 3 h. The aim of this study was to investigate possible mechanism(s) by which glucose infusion causes insulin resistance in skeletal muscle and in particular to examine whether this was associated with changes in insulin signaling. Hyperglycemia (~10 mM) was produced in cannulated male Wistar rats for up to 5 h. The glucose infusion rate required to maintain this hyperglycemia progressively lessened over 5 h (by 25%, P < 0.0001 at 5 h) without any alteration in plasma insulin levels consistent with the development of insulin resistance. Muscle glucose uptake in vivo (44%; P < 0.05) and glycogen synthesis rate (52%; P < 0.001) were reduced after 5 h compared with after 3 h of infusion. Despite these changes, there was no decrease in the phosphorylation state of multiple insulin signaling intermediates [insulin receptor, Akt, AS160 (Akt substrate of 160 kDa), glycogen synthase kinase-3beta] over the same time course. In isolated soleus strips taken from control or 1- or 5-h glucose-infused animals, insulin-stimulated 2-deoxyglucose transport was similar, but glycogen synthesis was significantly reduced in the 5-h muscle sample (68% vs. 1-h sample; P < 0.001). These results suggest that the reduced muscle glucose uptake in rats after 5 h of acute hyperglycemia is due more to the metabolic effects of excess glycogen storage than to a defect in insulin signaling or glucose transport.

Glucokinase Thermolability and Hepatic Regulatory Protein Binding Are Essential Factors for Predicting the Blood Glucose Phenotype of Missense Mutations

To better understand how glucokinase (GK) missense mutations associated with human glycemic diseases perturb glucose homeostasis, we generated and characterized mice with either an activating (A456V) or inactivating (K414E) mutation in the gk gene. Animals with these mutations exhibited alterations in their blood glucose concentration that were inversely related to the relative activity index of GK. Moreover, the threshold for glucose-stimulated insulin secretion from islets with either the activating or inactivating mutation were left- or right-shifted, respectively. However, we were surprised to find that mice with the activating mutation had markedly reduced amounts of hepatic GK activity. Further studies of bacterially expressed mutant enzymes revealed that GK(A456V) is as stable as the wild type enzyme, whereas GK(K414E) is thermolabile. However, the ability of GK regulatory protein to inhibit GK(A456V) was found to be less than that of the wild type enzyme, a finding consistent with impaired hepatic nuclear localization. Taken together, this study indicates that it is necessary to have knowledge of both thermolability and the interactions of mutant GK enzymes with GK regulatory protein when attempting to predict in vivo glycemic phenotypes based on the measurement of enzyme kinetics.

Key Role for Ceramides in Mediating Insulin Resistance in Human Muscle Cells

Elevated non-esterified fatty acids, triglyceride, diacylglycerol, and ceramide have all been associated with insulin resistance in muscle. We set out to investigate the role of intramyocellular lipid metabolites in the induction of insulin resistance in human primary myoblast cultures. Muscle cells were subjected to adenovirus-mediated expression of perilipin or incubated with fatty acids for 18 h, prior to insulin stimulation and measurement of lipid metabolites and rates of glycogen synthesis. Adenovirus-driven perilipin expression lead to significant accumulation of triacylglycerol in myoblasts, without any detectable effect on insulin sensitivity, as judged by the ability of insulin to stimulate glycogen synthesis. Similarly, incubation of cells with the monounsaturated fatty acid oleate resulted in triacylglycerol accumulation without inhibiting insulin action. By contrast, the saturated fatty acid palmitate induced insulin resistance. Palmitate treatment caused less accumulation of triacylglycerol than did oleate but also induced significant accumulation of both diacylglycerol and ceramide. Insulin resistance was also caused by cell-permeable analogues of ceramide, and palmitate-induced resistance was blocked in the presence of inhibitors of de novo ceramide synthesis. Oleate co-incubation completely prevented the insulin resistance induced by palmitate. Our data are consistent with ceramide being the agent responsible for insulin resistance caused by palmitate exposure. Furthermore, the triacylglycerol derived from oleate was able to exert a protective role in sequestering palmitate, thus preventing its conversion to ceramide.

Effect of moderate fat/high sucrose diet on glycogen synthesis rates in rat skeletal muscle upon the cessation of voluntary wheel running

Voluntary wheel running (VWR) (21 days; 6 km/night) rats display enhanced skeletal muscle insulin sensitivity in vitro which quickly decreases to sedentary levels after the cessation of running for...

Application of Protein or Protein Hydrolysates to Improve Postexercise Recovery

Protein, protein hydrolysates, and amino acids have become popular ingredients in sports nutrition. The use of protein, protein hydrolysates, and amino acid mixtures has multiple applications when aiming to improve postexercise recovery. After exhaustive endurance-type exercise, muscle glycogen repletion is the most important factor determining the time needed to recover. Coingestion of relatively small amounts of protein and/or amino acids with carbohydrate can be used to augment postprandial insulin secretion and accelerate muscle glycogen synthesis rates. Furthermore, it has been well established that ingesting protein, protein hydrolysates, and amino acid can stimulate protein synthesis and inhibit protein breakdown and, as such, improve net muscle protein balance after resistance- or endurance-type exercise. The latter has been suggested to lead to a more effective adaptive response to each successive exercise bout. To augment net muscle protein accretion, athletes involved in resistance-type exercise generally ingest both protein and carbohydrate during postexercise recovery. However, carbohydrate ingestion after resistance-type exercise does not seem to be warranted to further stimulate muscle protein synthesis or improve whole-body protein balance when ample protein has already been ingested. Because resistance-type exercise is also associated with a substantial reduction in muscle glycogen content, it would be preferred to coingest some carbohydrate when aiming to accelerate glycogen repletion. More research is warranted to assess the impact of ingesting different proteins, protein hydrolysates, and/or amino acids on muscle protein accretion after exercise.

P38 mitogen-activated protein kinase mediates adenosine-induced alterations in myocardial glucose utilization via 5′-AMP-activated protein kinase

Adenosine-induced acceleration of glycolysis in hearts stressed by transient ischemia is accompanied by suppression of glycogen synthesis and by increases in activity of adenosine 5'-monophosphate-activated protein kinase (AMPK). Because p38 mitogen-activated protein kinase (MAPK) may regulate glucose metabolism and may be activated downstream of AMPK, this study determined the effects of the p38 MAPK inhibitors SB202190 and SB203580 on adenosine-induced alterations in glucose utilization and AMPK activity. Studies were performed in working rat hearts perfused aerobically following stressing by transient ischemia (2 x 10-min ischemia followed by 5-min reperfusion). Phosphorylation of AMPK and p38 MAPK each were increased fourfold by adenosine, and these effects were inhibited by either SB202190 or SB203580. Neither of these inhibitors directly affected AMPK activity. Attenuation of the adenosine-induced increase in AMPK and p38 MAPK phosphorylation by SB202190 and SB203580 occurred independently of any change in tissue ATP-to-AMP ratio and did not alter glucose uptake, but it was accompanied by an increase in glycogen synthesis and glycogen content and by inhibition of glycolysis and proton production. There was a significant inverse correlation between the rate of glycogen synthesis and AMPK activity and between AMPK activity and glycogen content. These data demonstrate that AMPK is likely downstream of p38 MAPK in mediating the effects of adenosine on glucose utilization in hearts stressed by transient ischemia. The ability of p38 MAPK inhibitors to relieve the inhibition of glycogen synthesis and to inhibit glycolysis and proton production suggests that these agents may restore adenosine-induced cardioprotection in stressed hearts.

Effects of Chromium Supplementation on Glycogen Synthesis after High-Intensity Exercise

Chromium enhances insulin signaling and insulin-mediated glucose uptake in cultured cells. We investigated the effect of chromium on glycogen synthesis and insulin signaling in humans. Sixteen overweight men (BMI = 31.1 +/- 3.0 kg.m) were randomly assigned to supplement with 600 microg.d chromium as picolinate (Cr; N = 8) or a placebo (Pl; N = 8). After 4 wk of supplementation, subjects performed a supramaximal bout of cycling exercise to deplete muscle glycogen, which was followed by high-glycemic carbohydrate feedings for the next 24 h. Muscle biopsies were obtained at rest, immediately after exercise, and 2 and 24 h after exercise. Elevations in glucose and insulin during recovery were not different, but the lactate response was significantly higher in Cr. There was a significant depletion in glycogen immediately after exercise, an increase at 2 h, and a further increase above rest at 24 h (P < 0.05). The rate of glycogen synthesis during the 2 h after exercise was not different between groups (Cr: 25.8 +/- 8.0 and Pl: 17.1 +/- 4.7 mmol.kg.h). Glycogen synthase activity was significantly increased immediately after exercise in both groups. Muscle phosphatidylinositol 3-kinase (PI 3-kinase) activity decreased immediately after exercise and increased at 2 h (P < 0.05), with a trend for a lower PI 3-kinase response in Cr (P = 0.08). Chromium supplementation did not augment glycogen synthesis during recovery from high-intensity exercise and high-carbohydrate feeding, although there was a trend for lower PI 3-kinase activity.

Immunoneutralization of Endogenous Glucagon Reduces Hepatic Glucose Output and Improves Long-Term Glycemic Control in Diabetic ob/ob Mice

In type 2 diabetes, glucagon levels are elevated in relation to the prevailing insulin and glucose levels. The relative hyperglucagonemia is linked to increased hepatic glucose output (HGO) and hyperglycemia. Antagonizing the effects of glucagon is therefore considered an attractive target for treatment of type 2 diabetes. In the current study, effects of eliminating glucagon signaling with a glucagon monoclonal antibody (mAb) were investigated in the diabetic ob/ob mouse. Acute effects of inhibiting glucagon action were studied by an oral glucose tolerance test (OGTT) and by measurement of HGO. In addition, the effects of subchronic (5 and 14 days) glucagon mAb treatment on plasma glucose, insulin, triglycerides, and HbA1c (A1C) levels were investigated. Glucagon mAb treatment reduced the area under the curve for glucose after an OGTT, reduced HGO, and increased the rate of hepatic glycogen synthesis. Glucagon mAb treatment for 5 days lowered plasma glucose and triglyceride levels, whereas 14 days of glucagon mAb treatment reduced A1C. In conclusion, acute and subchronic neutralization of endogenous glucagon improves glycemic control, thus supporting the contention that glucagon antagonism may represent a beneficial treatment of diabetes.

Short-term activation of peroxysome proliferator-activated receptor β/δ increases fatty acid oxidation but does not restore insulin action in muscle cells from type 2 diabetic patients

Defective fatty acid oxidation in skeletal muscle is one of the possible causes of insulin resistance. Peroxisome proliferator-activated receptor beta activators are strong inducers of fatty acid oxidation. The aim of this study was to verify whether activation of fatty acid oxidation by PPARbeta agonists in human skeletal muscle cells prepared from type 2 diabetic patients could improve the reduced responses to insulin that characterized this cell model. GW0742 (10 nM) significantly increased fatty acid oxidation and oxidative gene expression in myotubes prepared from both healthy subjects and type 2 diabetic patients. In cells from control subjects, incubation with the agonist for 48 h affected neither insulin-induced rate of glycogen synthesis nor the phosphorylation state of protein kinase B (PKB serine 473). Myotubes from type 2 diabetic patients displayed marked reduction in the effects of insulin on glycogen synthesis and on PKB phosphorylation. However, treatment with PPARbeta agonists did not restore these defects. Therefore, these results indicate that induction of fatty acid oxidation with PPARbeta activators during short-term exposition is not sufficient to correct for insulin resistance in muscle cells from type 2 diabetic patients. This suggests that additional studies are needed to better characterize the link between fatty acid oxidation and insulin sensitivity in humans.

Inhibition of Insulin-Stimulated Glycogen Synthesis by 5-Aminoimidasole-4-Carboxamide-1-β-d-Ribofuranoside-Induced Adenosine 5′-Monophosphate-Activated Protein Kinase Activation: Interactions with Akt, Glycogen Synthase Kinase 3-3α/β, and Glycogen Synthase in Isolated Rat Soleus Muscle

The aim of this study was to investigate the effects of 5-aminoimidasole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-induced AMP-activated protein kinase activation on glycogen metabolism in soleus (slow twitch, oxidative) and epitrochlearis (fast twitch, glycolytic) skeletal muscles. Isolated soleus and epitrochlearis muscles were incubated in the absence or presence of insulin (100 nM), AICAR (2 mM), and AICAR plus insulin. In soleus muscles exposed to insulin, glycogen synthesis and glycogen content increased 6.4- and 1.3-fold, respectively. AICAR treatment significantly suppressed ( approximately 60%) insulin-stimulated glycogen synthesis and completely prevented the increase in glycogen content induced by insulin. AICAR did not affect either basal or insulin-stimulated glucose uptake but significantly increased insulin-stimulated ( approximately 20%) lactate production in soleus muscles. Interestingly, basal glucose uptake was significantly increased ( approximately 1.4-fold) in the epitrochlearis muscle, even though neither basal nor insulin-stimulated rates of glycogen synthesis, glycogen content, and lactate production were affected by AICAR. We also report the novel evidence that AICAR markedly reduced insulin-induced Akt-Thr308 phosphorylation after 15 and 30 min exposure to insulin, which coincided with a marked reduction in glycogen synthase kinase 3 (GSK)-3alpha/beta phosphorylation. Importantly, phosphorylation of glycogen synthase was increased by AICAR treatment 45 min after insulin stimulation. Our results indicate that AICAR-induced AMP-activated protein kinase activation caused a time-dependent reduction in Akt308 phosphorylation, activation of glycogen synthase kinase-3alpha/beta, and the inactivation of glycogen synthase, which are compatible with the acute reduction in insulin-stimulated glycogen synthesis in oxidative but not glycolytic skeletal muscles.

The effect of glutamine and dihydroxyacetone supplementation on food intake, weight gain, and postprandial glycogen synthesis in female Zucker rats

Objective We sought to test the hypothesis that increasing postprandial hepatic glycogen synthesis rate would decrease food intake and growth rate in obese Zucker rats. Design Supplements of glutamine, with and without dihydroxyacetone (DHA), which have previously been shown to stimulate hepatic glycogen synthesis, were administered in the diet of obese Zucker rats for periods of 1 and 3 wk. Measurements Food intake and body weight were monitored throughout the experiments. At the end of the feeding period the rats were fed a test meal and injected with 3H 2O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose and triacylglycerol and hepatic glycogen content were also determined. Carcass fat and water contents were also measured in the 3-wk study. Results Dietary glutamine had no effect on food intake, weight gain, or body composition. Addition of DHA caused a reduction in food intake and weight gain and a stimulation of in vivo hepatic glycogen synthesis after 1 wk, but these changes were abolished by the end of 3 wk. Hepatic lipogenesis in vivo was increased by DHA treatment for 1 and 3 wk. Conclusions Stimulation of hepatic glycogen synthesis by DHA treatment was associated with a reduction in food intake. However, the effect of DHA on glycogen synthesis and food intake disappeared after 3 wk of supplementation.

Contraction Activates Glycogen Synthase Independently of Initial Glycogen Concentration

Muscle contraction activates glycogen synthesis, but the mechanism for activation of glycogen synthase after contractile activity is poorly understood. Glycogen concentration is powerful regulator of glycogen synthase and it has been suggested that reduced glycogen content determines activation of glycogen synthase after contractile activity. PURPOSE: The purpose of the present study was to investigate effects of muscle contraction on glycogen synthesis, glycogen synthase activation and glycogen synthase phosphorylation in muscle with different glycogen concentrations. METHODS: We manipulated the muscle glycogen content to low (94.8 ±5.0 mmol-kg−1; 24-hours fasted rats; n=36), normal (203.8±10.2 mmol-kg1; Free access to chow; n=28), and high (459.3±30.9 mmol-kg−1; 24-hours fasted rats were refed for 24 hours to supercompensate glycogen; n=32). After manipulation, muscles were dissected for in vitro studies, mounted on contraction apparatus, and stimulated electrically for 30 min. Subsequently, glycogen synthesis, glycogen synthase activity, and glycogen synthase Ser645, Ser649, Ser653, Ser657 phosphorylation were assessed. RESULTS: Contraction decreased glycogen content by 120.6±4.7 (n=28) and 131.5±8.4 mmol-kg−1 (n=32) in muscles with normal and high glycogen, respectively. In muscles with low glycogen, glycogen breakdown was reduced to 67.4±5.0 mmol-kg−1(p<0.001; n=28). Rate of glycogen synthesis after contraction was inversely correlated to initial glycogen content. Contraction increased GS activity in all groups (p < 0.001). Interestingly, contraction activated glycogen synthase in muscles with high glycogen (p < 0.01) without dephosphorylation of the sites phosphorylated by GSK-3. Contraction dephosphorylated these sites in muscles with low and normal glycogen. When insulin was present after contraction, an additive effect of insulin on glycogen synthesis and glycogen synthase activation. Interestingly, rate of glycogen synthesis reach the same level in muscles with low and normal glycogen when insulin was present after contraction; so did glycogen synthase fractional activity and glycogen synthase Ser645, Ser649, Ser653, Ser657 phosphorylation. CONCLUSION: Contractile activity is a powerful activator of GS and glycogen synthesis even in muscles high glycogen content. In muscles with high glycogen, glycogen synthase fractional activity was increased without dephosphorylation of the sites phosphorylated by GSK-3, indicating that contraction activates glycogen synthase by dephosphorylation of other sites. Supported by the Research Council of Norway and The Novo Nordisk Foundation.

Effects of adenosine on myocardial glucose and palmitate metabolism after transient ischemia: role of 5′-AMP-activated protein kinase

Loss of cardioprotection by adenosine in hearts stressed by transient ischemia may be due to its effects on glucose metabolism. In the absence of transient ischemia, adenosine inhibits glycolysis, whereas it accelerates glycolysis after transient ischemia. Inasmuch as 5'-AMP-activated protein kinase (AMPK) is implicated as a regulator of glucose and fatty acid utilization, this study determined whether a differential alteration of AMPK activity contributes to acceleration of glycolysis by adenosine in hearts stressed by transient ischemia. Studies were performed in working rat hearts perfused aerobically under normal conditions or after transient ischemia (two 10-min periods of ischemia followed by 5 min of reperfusion). LV work was not affected by adenosine. AMPK phosphorylation was not affected by transient ischemia; however, phosphorylation and activity were increased nine- and threefold, respectively, by adenosine in stressed hearts. Phosphorylation of acetyl-CoA carboxylase and rates of palmitate oxidation were unaltered. Glycolysis and calculated proton production were increased 1.8- and 1.7-fold, respectively, in hearts with elevated AMPK activity. Elevated AMPK activity was associated with inhibition of glycogen synthesis and unchanged rates of glucose uptake and glycogenolysis. Phentolamine, an alpha-adrenoceptor antagonist, which prevents adenosine-induced activation of glycolysis in stressed hearts, prevented AMPK phosphorylation. These data demonstrate that adenosine-induced activation of AMPK after transient ischemia is not sufficient to alter palmitate oxidation or glucose uptake. Rather, activation of AMPK alters partitioning of glucose away from glycogen synthesis; the increase in glycolysis may in part contribute to loss of adenosine-induced cardioprotection in hearts subjected to transient ischemia.

Knocking out pyruvate dehydrogenase kinase 4 lowers blood glucose by altering fuel selection in peripheral tissues

Activity of the pyruvate dehydrogenase complex (PDC) is strongly inhibited by phosphorylation in the fasted state and by diabetes. An important component of the mechanism, greater pyruvate dehydrogenase kinase 4 (PDK4) activity due to increased expression, was investigated with PDK4-knockout (PDK4-KO) mice. Mice that lack PDK4 exhibit modestly lower fasting blood glucose and improved glucose tolerance. Activity state of PDC (% of complex dephosphorylated and active) is greater in heart, skeletal muscle, and kidney but not the liver of fasted PDK4-KO mice. Concentrations of the intermediates of the gluconeogenic pathway are reduced in the liver of PDK4-KO mice, consistent with a reduced rate of gluconeogenesis due to a substrate supply limitation. The blood concentrations of gluconeogenic substrates are reduced in PDK4-KO mice, consistent with reduced formation in peripheral tissues. Lactate, pyruvate, and alanine are formed at slower rates by isolated muscle preparations from PDK4-KO mice as a consequence of increased oxidation of glucose to CO2, reduced glycolysis, and a greater rate of glycogen synthesis. Catabolism of branched-chain amino acids (BCAAs) is reduced in muscle preparations at the level of transamination with α-ketoglutarate, consistent with the importance of BCAAs as a major source of amino groups for alanine synthesis. Fasting induces higher blood levels of free fatty acids in PDK4-KO mice than in normal mice. This is explained by a slower rate of fatty acid oxidation in the muscle of PDK4-KO mice, a consequence of increased rates of glucose and pyruvate oxidation. These findings confirm the importance of upregulation of PDK4 for glucose homeostasis and support PDK4 as a therapeutic target for diabetes. Supported by DK47844 and the American Diabetes Association.

Postprandial glycogen and lipid synthesis in prednisolone-treated rats maintained on high-protein diets with varied carbohydrate levels

Objective The present experiment was designed to study the effect of a high-protein, high-carbohydrate diet versus a high-protein, low-carbohydrate diet on in vivo postprandial glycogen and lipid synthesis of rats treated with prednisolone. Methods Thirty-two 6-wk-old male Sprague-Dawley rats were randomly assigned to one of four equal groups: high-protein, high-carbohydrate; high-protein, high-carbohydrate with prednisolone; high-protein, low-carbohydrate; and high-protein, low-carbohydrate with prednisolone. Rats were sham operated or subcutaneously implanted with prednisolone pellets while being maintained on their respective diets (39% of energy from protein) for 6 wk. Food intake and body weight were monitored throughout the experiment. At the end of the feeding period, overnight-fasted rats were fed a test meal and injected with 3H 2O to measure in vivo rates of glycogen and lipid synthesis. Final plasma glucose, insulin, and triacylglycerol concentrations and hepatic glycogen content were also measured. Results Results showed that hepatic glycogen content (milligrams per gram of liver) was similar across all four experimental groups. Total hepatic glycogen synthesis and its percentage synthesis via pyruvate (indirect pathway) were higher in rats maintained on the high-protein, high-carbohydrate diet compared with those on the high-protein, low-carbohydrate diet and this was not substantially affected by prednisolone administration. Hepatic and epididymal fat pad lipid syntheses were not altered by diet or prednisolone treatments. Conclusion Under long-term high-protein conditions, prednisolone administration does not seem to affect hepatic glycogen synthesis, which was increased with the increased carbohydrate content of the diet.

Using Recovery Modalities between Training Sessions in Elite Athletes

Achieving an appropriate balance between training and competition stresses and recovery is important in maximising the performance of athletes. A wide range of recovery modalities are now used as integral parts of the training programmes of elite athletes to help attain this balance. This review examined the evidence available as to the efficacy of these recovery modalities in enhancing between-training session recovery in elite athletes. Recovery modalities have largely been investigated with regard to their ability to enhance the rate of blood lactate removal following high-intensity exercise or to reduce the severity and duration of exercise-induced muscle injury and delayed onset muscle soreness (DOMS). Neither of these reflects the circumstances of between-training session recovery in elite athletes. After high-intensity exercise, rest alone will return blood lactate to baseline levels well within the normal time period between the training sessions of athletes. The majority of studies examining exercise-induced muscle injury and DOMS have used untrained subjects undertaking large amounts of unfamiliar eccentric exercise. This model is unlikely to closely reflect the circumstances of elite athletes. Even without considering the above limitations, there is no substantial scientific evidence to support the use of the recovery modalities reviewed to enhance the between-training session recovery of elite athletes. Modalities reviewed were massage, active recovery, cryotherapy, contrast temperature water immersion therapy, hyperbaric oxygen therapy, nonsteroidal anti-inflammatory drugs, compression garments, stretching, electromyostimulation and combination modalities. Experimental models designed to reflect the circumstances of elite athletes are needed to further investigate the efficacy of various recovery modalities for elite athletes. Other potentially important factors associated with recovery, such as the rate of post-exercise glycogen synthesis and the role of inflammation in the recovery and adaptation process, also need to be considered in this future assessment.

Central Role for Protein Targeting to Glycogen in the Maintenance of Cellular Glycogen Stores in 3T3-L1 Adipocytes

Overexpression of the protein phosphatase 1 (PP1) subunit protein targeting to glycogen (PTG) markedly enhances cellular glycogen levels. In order to disrupt the endogenous PTG-PP1 complex, small interfering RNA (siRNA) constructs against PTG were identified. Infection of 3T3-L1 adipocytes with PTG siRNA adenovirus decreased PTG mRNA and protein levels by >90%. In parallel, PTG reduction resulted in a >85% decrease in glycogen levels 4 days after infection, supporting a critical role for PTG in glycogen metabolism. Total PP1, glycogen synthase, and GLUT4 levels, as well as insulin-stimulated signaling cascades, were unaffected. However, PTG knockdown reduced glycogen-targeted PP1 protein levels, corresponding to decreased cellular glycogen synthase- and phosphorylase-directed PP1 activity. Interestingly, GLUT1 levels and acute insulin-stimulated glycogen synthesis rates were increased two- to threefold, and glycogen synthase activation in the presence of extracellular glucose was maintained. In contrast, glycogenolysis rates were markedly increased, suggesting that PTG primarily acts to suppress glycogen breakdown. Cumulatively, these data indicate that disruption of PTG expression resulted in the uncoupling of PP1 activity from glycogen metabolizing enzymes, the enhancement of glycogenolysis, and a dramatic decrease in cellular glycogen levels. Further, they suggest that reduction of glycogen stores induced cellular compensation by several mechanisms, but ultimately these changes could not overcome the loss of PTG expression.

The glycaemic index and sports nutrition

Carbohydrate (CHO) is the main fuel for exercising muscles, therefore the amount, timing and type of CHO food ingested is an important part of an athlete’s daily dietary intake. The amount and timing of CHO ingestion has been investigated extensively. It has been suggested that the glycaemic index (GI) of CHO foods influences CHO availability during exercise and the rate of glycogen synthesis post-exercise. Although low-GI (LGI) CHO foods are mostly recommended for the pre-exercise meal, ingesting high-GI (HGI) CHO foods pre-exercise mostly does not result in hypoglycaemia in healthy individuals during exercise. HGI and LGI CHO foods yield similar results in terms of exercise performance and perceived rate of exertion. HGI and moderate GI (MGI) CHO foods are recommended during exercise. However, fructose in high concentrations is not recommended owing to increased risk of gastrointestinal distress. LGI CHO foods are not recommended during a short recovery period (< 6 hours) because of their slow rate of absorption and indigestible CHO, which seems to be a poor substrate for glycogen synthesis.

Sources of plasma glucose and liver glycogen in fasted ob/ob mice

Alterations in intrahepatic carbohydrate fluxes in ob/ob mice and the effects of acute leptin administration were studied in vivo by use of a dual-isotope tracer infusion. Metabolic sources of plasma glucose (gluconeogenesis (GNG) and glycogenolysis) and hepatic glycogen (GNG, direct synthesis and pre-existing) were determined in 20-h-fasted mice infused with [2-13C1]glycerol and [U13C6]glucose for 3 h. Total glucose output (TGO) and the rate of appearance (Ra) of plasma glycerol were measured by isotope dilution. GNG, the direct pathway of hepatic glycogen synthesis and hepatic triose-phosphate flux were determined by mass isotopomer distribution analysis (MIDA). Serum glucose, insulin, leptin and liver glycogen concentrations were also measured. After a 24-h fast, ob/ob mice had 2-fold higher TGO, 2.5-fold elevated liver glycogen content and markedly higher glycogenolytic flux to glucose, absolute GNG and direct glycogen synthesis rates (10-fold increased) compared to the control group. Ob/ob mice also had elevated triose-phosphate flux compared to controls (40 vs. 22 mg/kg lean body mass/min). A model of intrahepatic flux distributions in control and ob/ob mice is presented. In summary, elevated fasting plasma glucose concentrations are due to increased TGO in ob/ob mice, which is maintained by both increased GNG and increased glycogenolysis. Furthermore, the ob/ob mice have major alterations in fasting hepatic carbohydrate fluxes into triose-phosphate pools and glycogen. We support the model that actions of leptin on hepatic glucose metabolism require insulin or other factors.