Glycogen breakdown -
Interestingly, insulin-stimulated PKB phosphorylation and activity was enhanced in muscle with low glycogen content Derave et al. However, we were unable to find elevated AS phosphorylation in muscles with reduced glycogen content despite that PKB phosphorylation was increased Lai et al.
Exercise increases insulin sensitivity but insulin signaling is not consistently improved after exercise see above. However, a consistent finding is that exercise decreases glycogen content Bergström et al. Glycogen breakdown has mostly been investigated after prolonged exercise, but high intensity also decreases glycogen content Esbjornsson-Liljedahl et al.
Interestingly, 2 weeks of HIT training has been reported to increase insulin sensitivity Richards et al. Exercise regulates insulin sensitivity via other mechanisms than reducing glycogen content.
Training increases GLUT4 content in skeletal muscles, which contributes to improved insulin sensitivity Houmard et al. A rather consistent finding is that glycogen content is higher in skeletal muscles from trained subjects and training increases glycogen content Burgomaster et al.
The glycogen stores are also refilled 24 h after exercise Costill et al. Indeed, the fact that glycogen content is increased in skeletal muscles after training may result from increased insulin sensitivity. From an evolutional point of view such increase in glycogen content may reflect an important adaptation: high skeletal muscles glycogen content improves the chance for survival in emergencies.
Decreasing glycogen content by exercise or fasting stimulates glycogen accumulation to levels above the glycogen content in well-fed conditions Hespel and Richter, ; Jensen et al. It is possible to increase the glycogen content in skeletal muscles if they are exposed to high concentrations of insulin and glucose Richter et al.
Why does glycogen content not increase when high amount of carbohydrates are ingested under normal physiological conditions?
Why is the excess carbohydrate ingested converted to lipid without elevation of glycogen content in skeletal muscles?
The glycogen content in skeletal muscles will reflects a balance between available glucose and insulin sensitivity in skeletal muscles. Studies in rats have under controlled conditions shown that training increases expression of GLUT4, but insulin sensitivity is not elevated in skeletal muscles because glycogen content also increases Kawanaka et al.
The acute adaptation to training is, therefore, higher glycogen content but stable insulin sensitivity. From an evolutional point of view, this indicates that high glycogen content is more important than high insulin sensitivity.
Prolonged training increases insulin sensitivity beyond the last training session, and insulin sensitivity correlates with oxidative capacity in skeletal muscles Bruce et al. GLUT4 expression in skeletal muscles also regulates insulin sensitivity and correlates with rate of glycogen resynthesis Hickner et al.
Interestingly, 24 h fasting GLUT4 content was elevated in fast-twitch epitrochlearis muscles where glycogen content was reduced Jensen et al. In soleus slow-twitch muscle , glycogen content was minimally affected by 24 h fasting and GLUT4 was unchanged Lai et al.
These findings support that replenishment of glycogen store is superior to elevated insulin sensitivity. Blood glucose concentration can be regulated in vivo even when skeletal muscle glycogen synthesis is impaired by short-term overeating Acheson et al. Genetic findings support that skeletal muscle glycogen synthesis is not an absolute requirement for regulation of blood glucose concentration.
Knockout mice lacking the skeletal muscle isoform of glycogen synthase have normal insulin sensitivity Pederson et al. In human, a child without glycogen synthase has been described, and also this person had a normal glucose response to an oral glucose tolerance test Kollberg et al.
Glycogen resynthesis is an important part of restitution after training and athletes optimize glycogen synthesis by intake of high amount of carbohydrates immediately after exercise Ivy, The energy source for rapid glycogen synthesis is blood glucose and rapid extraction of glucose from the blood is required for high rate of glycogen synthesis.
Diabetes subjects have impaired removal of blood glucose, because insulin-stimulated glycogen synthesis is impaired Shulman et al. Exercise-stimulated glycogen breakdown will stimulate skeletal muscle glycogen synthesis and extraction of blood glucose and increase insulin sensitivity.
Such increased insulin sensitivity may be secondary to replenishing glycogen stores in the context of survival. However, in the modern society, the increased insulin sensitivity after exercise may have its superior role to prevent development of insulin resistance and type 2 diabetes.
Glycogen content has a strong feedback inhibition of glycogen synthase activity Danforth, and the glycogen stores are limited. It is not possible to dispose glucose into glycogen when stores are filled and under such condition, glucose remains in the blood until it is utilized as energy or transformed into lipid.
Skeletal muscles have a crucial role for regulation of whole body glucose metabolism, but acute elevation of glycogen does not impair insulin signaling and insulin-stimulated glucose transport may be normal Jensen et al.
However, insulin-stimulated glycogen synthesis is decreased, and more glucose is metabolized via glycolysis and we suggest that such increased glucose metabolism in skeletal muscles is unhealthy. Insulin signaling and insulin-stimulated glucose transport are impaired in muscles from rats and humans showing manifest insulin resistance or type 2 diabetes Etgen et al.
However, such insulin resistance develops gradually. The mechanisms for development of insulin resistance in skeletal are not well-understood, but accumulation of lipid and lipid intermediates are likely contributors Aas et al. Furthermore, energy surplus increases production of reactive oxidative spices Hoehn et al.
The production of ROS is increased when high amount of glucose and fat is supplied the mitochondria simultaneously and forces electrons into the electron transport chain Hue and Taegtmeyer, Preventing ROS production in skeletal muscles protects skeletal muscles form developing insulin resistance Hoehn et al.
Insulin resistant muscles are characterized with numerous changes e. In skeletal muscles with low glycogen, glucose will be stored as muscles glycogen Ivy, ; Hickner et al.
A major concern for athletes after strenuous training is to replete the glycogen stores is skeletal muscles preparing for new training sessions or competitions. Skeletal muscles are able to extract blood glucose effectively when high amount of carbohydrate are supplied Ivy, , and we suggest that glucose disposal into skeletal muscle glycogen is healthy storage of carbohydrates.
Indeed, healthy humans have large capacity to store glucose as lipid Figure 2. Acheson et al. Importantly, de novo lipid synthesis occurred without development of hyperglycemia, but blood triglyceride content increased fold Acheson et al. Accumulation of fat per se does not cause insulin resistance Haemmerle et al.
Figure 2. Excess energy intake is stored after meals as glycogen and triacylglycerols. Carbohydrate can be stored as glycogen mainly in skeletal muscles or the liver; fat is manly stores as triacylglycerol in adipose tissue. With filled glycogen stores, glucose can be the substrate for de novo lipid synthesis and stored in adipocytes, muscles, or the liver and cause insulin resistance.
Glycogen and fat are important energy substrates during exercise. Accumulation of lipid intermediates seems to occur secondary to increased glycogen content and acute exercise reduces lipid synthesis during glucose loads Figure 2.
Moreover, it has been reported that insulin resistant subjects stores a larger part of ingested glucose as lipid in skeletal muscles and liver compared to insulin sensitive subjects, whereas skeletal muscles glycogen synthesis is lower in insulin resistant subjects Petersen et al.
A reduced capacity to store glucose as glycogen promotes de novo lipogenesis, which will deteriorate of insulin sensitivity due to lipid accumulation. In the modern society, abundant food and inactivity are large challenges for humans, and metabolic diseases related to obesity deteriorate public health.
Although the improved insulin sensitivity after glycogen depleting exercise may not have evolved to improve regulation of blood glucose, such effect of exercise may be the mechanism that protect humans from developing type 2 diabetes in the modern society.
We suggest that dynamic glycogen metabolism is important for healthy regulation of blood glucose and prevention of insulin resistance.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Aas, V. Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycaemia. Acta Physiol. Pubmed Abstract Pubmed Full Text CrossRef Full Text. Acheson, K. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Pubmed Abstract Pubmed Full Text.
Alessi, D. Mechanism of activation and function of protein kinase B. Arias, E. Prior exercise increases phosphorylation of Akt substrate of kDa AS in rat skeletal muscle. Aslesen, R. Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols.
Effects of epinephrine on glucose metabolism in contracting rat skeletal muscle. Åstrand, P. Textbook of Work Physiology. New York: McGraw-Hill Book Company, 1— Bergström, J. Diet, muscle glycogen and physical performance.
Muscle glycogen synthesis after exercise: an enhancing factor localized to the muscle cells in man. Nature , — Betts, J. Short-term recovery from prolonged exercise: exploring the potential for protein ingestion to accentuate the benefits of carbohydrate supplements.
Sports Med. Boushel, R. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans. Mitochondrion 11, — Bouskila, M. Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle.
Cell Metab. Brady, M. Allosteric trumps covalent in the control of glycogen synthesis. Bruce, C. Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status. Burgomaster, K.
Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans. Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. Cartee, G. Prolonged increase in insulin-stimilated glucose transport in muscle after exercise.
Chasiotis, D. Regulation of glycogenolysis in human muscle in response to epinephrine infusion. Christ, C. Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.
Christ-Roberts, C. Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53, — Cleasby, M. Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression.
Cohen, P. Dissection of the protein phosphorylation cascades involved in insulin and growth factor action. The origins of protein phosphorylation. Cell Biol. Connett, R. Exercise: Regulation and Integration of Multiple System , eds L.
Rowell and J. Shepherd Bethesda, MD: American Physiological Society , — Cori, C. The mechanism of epinephrine action. The influence of epinephrine on the carbohydrate metabolism of fasting rats, with a note on new formation of carbohydrates.
Costill, D. The role of dietary carbohydrates in muscle glycogen resynthesis after strenuous running. Coyle, E. Muscle glycogen utilization during prolonged strenuous exercise when fed carbohydrate. Danforth, W. Glycogen synthase activity in skeletal muscle.
DeFronzo, R. Synergistic interaction between exercise and insulin on peripheral glucose uptake. CrossRef Full Text. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 30, — Dela, F. GLUT 4 and insulin receptor binding and kinase activity in trained human muscle.
Derave, W. Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity. Contraction-stimulated muscle glucose transport and GLUT-4 surface content are dependent on glycogen concentration.
Esbjornsson-Liljedahl, M. Smaller muscle ATP reduction in women than in men by repeated bouts of sprint exercise. Metabolic response in type I and type II muscle fibers during a s cycle sprint in men and women. Etgen, G.
Exercise training reverses insulin resistance in muscle by enhanced recruitment of GLUT-4 to the cell surface.
Glucose transport and cell surface GLUT-4 protein in skeletal muscle of the obese Zucker rat. Franch, J. Regulation of glycogen synthesis in rat skeletal muscle after glycogen depleting contractile activity: effects of adrenaline on glycogen synthesis and activation of glycogen synthase and glycogen phosphorylase.
Acyl-CoA binding protein expression is fibre type specific and elevated in muscles from obese insulin-resistant Zucker rat. Diabetes 51, — Frayn, K. Calculation of substrate oxidation rates in vivo from gaseous exchange.
Frosig, C. Effects of endurance exercise training on insulin signaling in human skeletal muscle: interactions at the level of phosphatidylinositol 3-kinase, Akt, and AS Diabetes 56, — Gibala, M.
Short-term sprint interval versus traditional endurance training: similar initial adaptations in human skeletal muscle and exercise performance.
Gjedsted, J. Effects of adrenaline on lactate, glucose, lipid and protein metabolism in the placebo controlled bilaterally perfused human leg. Greiwe, J. Effects of endurance exercise training on muscle glycogen accumulation in humans.
Haemmerle, G. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science , — Hawley, J. Carbohydrate-loading and exercise performance. An update. He, J.
Muscle glycogen content in type 2 diabetes mellitus. The branching of glycogen is an important feature of the molecule metabolically as well.
Since glycogen is broken down from the "ends" of the molecule, more branches translate to more ends, and more glucose that can be released at once. Breakdown of glycogen involves. Just as in gluconeogenesis, the cell has a separate mechanism for glycogen synthesis that is distinct from glycogen breakdown.
As noted previously, this allows the cell to separately control the reactions, avoiding futile cycles, and enabling a process to occur efficiently synthesis of glycogen that would not occur if it were simply the reversal of glycogen breakdown.
Synthesis of glycogen starts with G1P, which is converted to an 'activated' intermediate, UDP-glucose. This activated intermediate is what 'adds' the glucose to the growing glycogen chain in a reaction catalyzed by the enzyme known as glycogen synthase.
Once the glucose is added to glycogen, the glycogen molecule may need to have branches inserted in it by the enzyme known as branching enzyme. Glycogen phosphorylase sometimes simply called phosphorylase catalyzes breakdown of glycogen into GlucosePhosphate G1P.
The reaction, see above right that produces G1P from glycogen is a phosphorolysis, not a hydrolysis reaction. The distinction is that hydrolysis reactions use water to cleave bigger molecules into smaller ones, but phosphorolysis reactions use phosphate instead for the same purpose.
Note that the phosphate is just that - it does NOT come from ATP. Since ATP is not used to put phosphate on G1P, the reaction saves the cell energy. Glycogen phosphorylase will only act on non-reducing ends of a glycogen chain that are at least 5 glucoses away from a branch point.
A second enzyme, Glycogen Debranching Enzyme GDE , is therefore needed to convert alpha branches to alpha branches.
GDE acts on glycogen branches that have reached their limit of hydrolysis with glycogen phosphorylase. GDE acts to transfer a trisaccharide from a 1,6 branch onto an adjacent 1,4 branch, leaving a single glucose at the 1,6 branch. Note that the enzyme also catalyzes the hydrolysis of the remaining glucose at the 1,6 branch point.
Thus, the breakdown products from glycogen are G1P and glucose mostly G1P, however. Glucose can, of course, be converted to GlucosePhosphate G6P as the first step in glycolysis by either hexokinase or glucokinase. G1P can be converted to G6P by action of an enzyme called phosphoglucomutase.
This reaction is readily reversible, allowing G6P and G1P to be interconverted as the concentration of one or the other increases. This is important, because phosphoglucomutase is needed to form G1P for glycogen biosynthesis.
Regulation of glycogen metabolism is complex, occurring both allosterically and via hormone-receptor controlled events that result in protein phosphorylation or dephosphorylation. In order to avoid a futile cycle of glycogen synthesis and breakdown simultaneously, cells have evolved an elaborate set of controls that ensure only one pathway is primarily active at a time.
Regulation of glycogen metabolism is managed by the enzymes glycogen phosphorylase and glycogen synthase. Its regulation is consistent with the energy needs of the cell. High energy substrates ATP, G6P, glucose allosterically inhibit GP, while low energy substrates AMP, others allosterically activate it.
Glycogen phosphorylase exists in two different covalent forms — one form with phosphate called GPa here and one form lacking phosphate GPb here.
GPb is converted to GPa by phosphorylation by an enzyme known as phosphorylase kinase. GPa and GPb can each exist in an 'R' state and a 'T' state.
For both GPa and GPb, the R state is the more active form of the enzyme. GPa's negative allosteric effector glucose is usually not abundant in cells, so GPa does not. ip into the T state often. There is no positive allosteric effector of GPa, so when glucose is absent, GPa automatically flips into the R more active state.
In the rat, acute alcohol administration reduces the glucagon and catecholamine responses to stress Ethanol administration may also increase circulating acetate levels, which by itself may modulate the counterregulatory response to hypoglycemia Nevertheless, their estimation of the contribution of glycogen breakdown to the early phase of glucose counterregulation in normal subjects is borne out by our direct observations of the decrement in net hepatic glycogen.
This difference in hepatic glycogen could not be accounted for by differences in duration of fasting, because both the nondiabetic and the type 1 diabetic subjects were fasted overnight for the same duration before the study.
Additionally, the continuous insulin infusion administered to the type 1 diabetic subjects overnight would be expected to have increased baseline hepatic glycogen. These findings are in agreement with previous studies in less well-controlled type 1 diabetic subjects that demonstrated lower concentrations of hepatic glycogen in the postabsorptive state 13 , However, Bischof et al.
Thus, our finding of reduction of fasting hepatic glycogen content in intensively treated type 1 diabetic subjects will require further study. In addition to the apparent difference in fasting hepatic glycogen, we also observed dramatic differences in the time course of changes in hepatic glycogen during the clamp studies.
In type 1 diabetic subjects, there was no significant change in hepatic glycogen during either euglycemic or hypoglycemic studies.
These findings were in contrast to those observed in the nondiabetic subjects in whom hepatic glycogen fell during hypoglycemia. In concert with these data, EGP in type 1 diabetic subjects decreased proportionally during the euglycemic and hypoglycemic studies without any recovery even by the end of the hypoglycemic clamps.
The primary mechanism responsible for the lack of glycogen breakdown during hypoglycemia in type 1 diabetic subjects is likely due, at least in part, to the blunted hormonal counterregulatory response i. However, the significantly lower concentration of basal, fasting hepatic glycogen content in type 1 diabetic subjects even after overnight insulinization could also play a role in their defective glucose counterregulation.
Previous studies in type 1 diabetic subjects demonstrated defects in regulation of glycogenolysis and gluconeogenesis, although these experiments used different physiological paradigms 8 , 14 , 28 , Interestingly, Petersen et al. Consistent with these studies, the lack of change in hepatic glycogen that we observed in the type 1 diabetic subjects during hypoglycemia suggests that gluconeogenesis played the preponderant role in maintaining EGP during hypoglycemic counterregulation.
Although evidence of hepatic resistance to the effects of counterregulatory hormones is not strong, a recent report suggests attenuation of the effects of infused epinephrine on EGP in poorly controlled type 1 diabetes In contrast to these findings, Berk et al.
Alternatively, it is conceivable that the underlying mechanism that activates glycogen breakdown may be a combination of hormonal changes operative in the nondiabetic subjects but not present in type 1 diabetic subjects, i.
Finally, a potential role for the reduction in basal hepatic glycogen content cannot be excluded. In summary, these are the first direct measurements of hepatic glycogen content in nondiabetic subjects and in type 1 diabetic patients during insulin-induced hypoglycemia.
This decrease in liver glycogen suggests that glycogen breakdown is the major pathway contributing to the increased EGP for recovery of plasma glucose. In contrast, intensively treated patients with type 1 diabetes and defective hormonal counterregulation demonstrated no quantitative change in their liver glycogen content during hypoglycemia.
Our observations suggest that in type 1 diabetes, impaired counterregulatory hormone response, defects in baseline hepatic glycogen content, and the preponderant contribution of gluconeogenesis to EGP could all have an impact on the recovery of plasma glucose from insulin-induced hypoglycemia.
These defects may contribute to the recurrent episodes of severe hypoglycemia and possibly to the hypoglycemia-associated autonomic failure seen in intensively treated patients with type 1 diabetes. Proton-coupled 13 C NMR spectra from the liver. A : C-1 glycogen coupled with H-1 glycogen to form doublet at The inlayed trace is the zoomed C-1 glycogen doublet.
B : The time course spectra of glycogen at T1DM, type 1 diabetic subjects. EGP and rates of glucose uptake R d in nondiabetic subjects and type 1 diabetic subjects T1DM.
Percent change in hepatic glycogen averaged for the final 45 min of each clamp study in nondiabetic subjects and type 1 diabetic subjects. Plasma insulin, C-peptide, epinephrine, norepinephrine, and glucagon concentrations in nondiabetic and type 1 diabetic subjects. The costs of publication of this article were defrayed in part by the payment of page charges.
Section solely to indicate this fact. has received support from National Institutes of Health Grant KRR has received support from National Institutes of Health Grant RR has received support from National Institutes of Health Grant DK has received support from National Institutes of Health Grants DK and DK This work was supported by GCRC Grant MRR We are indebted to the staff of the GCRC and the Magnetic Resonance Research Center.
We thank Robin Sgueglia of the Diabetes Center Hormone Assay Core for plasma hormone determinations and Harsha Jayatillake, MS, and Daniel T. Stein, MD, for the isotopic enrichment assays performed in the GCRC Analytic Core Laboratory.
Parts of this study were presented in abstract form at the 64th annual meeting of the American Diabetes Association, Orlando, Florida, 4—8 June Sign In or Create an Account. Search Dropdown Menu. header search search input Search input auto suggest.
filter your search All Content All Journals Diabetes. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 55, Issue 3. Previous Article Next Article. RESEARCH DESIGN AND METHODS. Article Information. Article Navigation. Metabolism March 01 Role of Hepatic Glycogen Breakdown in Defective Counterregulation of Hypoglycemia in Intensively Treated Type 1 Diabetes Preeti Kishore ; Preeti Kishore.
This Site. Google Scholar. Ilan Gabriely ; Ilan Gabriely. Min-Hui Cui ; Min-Hui Cui. Joseph Di Vito ; Joseph Di Vito. Srikanth Gajavelli ; Srikanth Gajavelli. Jong-Hee Hwang ; Jong-Hee Hwang. Harry Shamoon Harry Shamoon. Address correspondence and reprint requests to Preeti Kishore, MD, Diabetes Research Center and Department of Medicine, Albert Einstein College of Medicine, Morris Park Ave.
E-mail: pkishore aecom. Diabetes ;55 3 —
Gkycogen 1-hour tutoring consultation Schedule Now. Allosteric regulation of Lice treatment for sensitive skin synthesis and Lice treatment for sensitive skin breakfown done by regulation of enzymes glycogen synthase and glycogen phosphorylase. Hormonal regulation of glycogen synthesis and breakdown is done by hormones insulin and glucagon. Glycogen synthase stimulates glycogen synthesis. Whenever the blood glucose level rises, the levels of glucosephosphate rises. Glucosephosphate stimulates glycogen synthase and thus glycogen synthesis occurs.Glycogen breakdown -
The overnight insulin infusion rate was adjusted according to an algorithm based on hourly blood glucose measurements, assuring a gradual normalization of plasma glucose levels.
The experimental protocol was initiated the following morning. Nondiabetic subjects were admitted to the GCRC for each experiment. Studies were performed after a h overnight fast. At on the day of study, two indwelling cannulas were inserted, one in an antecubital vein for infusions and the second in the contralateral forearm for blood sampling.
To obtain arterialized venous blood samples, this hand was maintained at 55°C with a nonmagnetic heating pad. Blood samples were obtained at min intervals for the determinations of plasma insulin, C-peptide, glucagon, epinephrine, and norepinephrine, as well as for glucose kinetics.
The enrichment of infused dextrose was kept equivalent to plasma glucose enrichment by addition of d -[6,6- 2 H 2 ]glucose to the infusate Plasma glucose was measured with a Beckman glucose analyzer Fullerton, CA using the glucose oxidase method.
Plasma d -[6,6- 2 H 2 ]glucose enrichment was measured using gas chromatography-mass spectrometry as previously described Calibration standards for d -[6,6- 2 H 2 ]glucose were made up from 0. All analyses were carried out with a 1-μl injection from an Agilent autoinjector into a gas chromatograph interfaced to a mass spectrometer using an Equity 5 gas chromatography column Supelco, Bellefone, PA.
The carrier gas was helium at 0. Sample peaks were integrated using the Chemstation integrator. The methods for measurement of plasma insulin, glucagon, epinephrine, norepinephrine, cortisol, and growth hormone and their intra- and interassay variations have been previously reported The RF coil was placed over the lateral aspect in the supine subject.
Initial coil placement was determined by percussing the borders of the liver, and the final position was confirmed by the image. To remove the signals from subcutaneous fat and muscle above the liver, a one-dimensional spectroscopic imaging method was used. The spectroscopic imaging acquisition parameters were as follows: a repetition time of 0.
The tip angle of o at the coil center was used for excitation. The field of view of Because the liver is located in an oblique fashion in the abdomen, the oblique localization was achieved by the simultaneous use of vertical and horizontal gradients.
A Gaussian-weighted phase-encoding scheme was used to improve the signal-to-noise ratios without sacrificing the efficiency of localization A total of phase-encoding steps over 32 k-space values was acquired per cycle of Gaussian-weighted sampling.
One data point of hepatic glycogen was acquired every 15 min. All spectroscopic imaging files were transferred from the Varian MR scanner to a personal computer. Each spectroscopic image was processed using customized programs in MATLAB MathWorks, Natick, MA.
Extracted spectroscopic imaging spectra from the liver were properly phased, and C-1 glycogen doublets were fitted to assess integrations of the glycogen peaks at A [ 13 C]formate sphere placed at the center of the 13 C coil served to calibrate the pulse angle and coil loading.
The integrated area of the glycogen Finally, individual variations in liver volume and shape were also corrected by image corrections. The liver outline of each subject determined from in vivo magnetic resonance imaging was superimposed on the pulse sequence image, and the relative ratio of those integrals was used as the correction factor to obtain the final concentrations of hepatic glycogen.
The intrasubject variability of the 13 C MR method was evaluated in control subjects using repeated hepatic glycogen measurements. Studies on the same and separate days were performed after an overnight fast.
The coefficients of variation for this method were 4. Glycogen measurements were acquired every 15 min during the euglycemic and hypoglycemic clamp.
Individual rates of net glycogenolysis were calculated by linear regression of the net glycogen concentration-time curves during each clamp 14 , Liver volume was quantified using liver volume MR imaging performed in a 1. Images were acquired with a phased array body coil in a Philips 1.
Three mm-thick images were obtained through the liver in a single breath hold, above the dome of diaphragm. The data were analyzed at a Philips EasyVision workstation for volumetric calculation using Philips software.
The capsular margins of liver were hand drawn with the workstation mouse, and the regions were evaluated with semiautomated volume calculation software. The liver volumes were averaged from three acquisitions for each subject.
The data in the text, figures, and tables are presented as means ± SE. Values for hormones, glucose infusion rate, EGP, and glucose uptake, obtained at min intervals, were also averaged over the final 30 min of each study. Rates of EGP were determined by subtracting rates of glucose infusion from the tracer-determined R a.
Figure 2 depicts the concentrations of plasma glucose in nondiabetic subjects and in the subjects with type 1 diabetes. The estimates of EGP and glucose uptake R d derived from isotopic analysis are depicted in Fig. Given the rates of insulin infusion used, hypoglycemia reached a stable plateau by 40 min in both groups.
An insulin infusion rate of 0. In marked contrast, in the type 1 diabetic subjects, there was no significant difference in EGP and R d related to hypoglycemic counterregulation between the euglycemic and hypoglycemic studies 1.
In the nondiabetic subjects, plasma insulin concentrations under baseline fasting conditions were comparable in both sets of studies Table 1.
With insulin infusion, plasma insulin was raised by 9- to fold and maintained at those levels. Although insulin was infused at identical rates in the two sets of studies, plasma insulin concentrations tended to be higher in the hypoglycemic studies the difference, however, was not significant.
In the type 1 diabetic subjects, basal plasma insulin levels were higher approximately sevenfold due to the overnight insulin infusion intended to maintain basal insulin requirements. However, during the final 30 min of the hypoglycemic clamps, plasma insulin was comparable within and between studies Table 1.
During euglycemia, the concentrations of all three counterregulatory hormones remained stable at baseline values in both groups Table 1. As expected, the glucagon response to hypoglycemia was absent, and the epinephrine response was markedly blunted in the type 1 diabetic subjects Table 1.
In all groups, liver volumes averaged 1, ± 60 ml before the initiation of the hypoglycemic studies and did not change significantly with hypoglycemia 1, ± 82 ml, NS. Figure 4 depicts the changes in hepatic glycogen concentrations estimated from NMR spectroscopy.
This value was significantly lower than that in overnight-fasted control subjects, despite identical periods of fasting. We examined the relative contribution of net hepatic glycogen content to the counterregulatory rise in EGP in nondiabetic subjects and in type 1 diabetic subjects during insulin-induced hypoglycemia.
We compared these parameters during euglycemia using the same insulin infusion rate and maintaining plasma glucose by a variable dextrose infusion. In concert with these data, the rates of EGP decreased proportionally during the euglycemic studies because of the suppressive effect of hyperinsulinemia on EGP, but activation of the counterregulatory hormones during hypoglycemia glucagon and epinephrine in particular contributed to the relative increase in EGP in the face of hyperinsulinemia.
Thus, the fluctuations in hepatic glycogen paralleled the rates of EGP both in the euglycemic and in the hypoglycemic studies. Because the influx of new glucose into the plasma glucose pool is assumed to be in a ratio with hepatic C1 glucosyl units, we used the decline in hepatic glycogen in millimoles per liter and the corresponding total liver volume to estimate EGP derived from glycogen over time.
Studies in animals demonstrated that epinephrine, a major component of the counterregulatory hormone response to hypoglycemia, induces a shift in glycogen metabolism toward glycogenolysis and, indirectly, toward an increase in gluconeogenesis by activating the peripheral delivery of gluconeogenic precursors to the liver Furthermore, glucagon released in response to hypoglycemia activates both glycogenolysis and gluconeogenesis 23 — 25 ; however, its effects on gluconeogenesis appear to be more persistent 9.
Taken together, these interactions that occur at the level of glycogen metabolism and gluconeogenesis act in concert to produce rapid recovery from insulin-induced hypoglycemia.
Lecavalier et al. Their findings also suggested that glycogenolysis represents the primary mechanism responsible for the increased EGP during hypoglycemia, followed by a sustained activation of gluconeogenesis.
The production of ROS is increased when high amount of glucose and fat is supplied the mitochondria simultaneously and forces electrons into the electron transport chain Hue and Taegtmeyer, Preventing ROS production in skeletal muscles protects skeletal muscles form developing insulin resistance Hoehn et al.
Insulin resistant muscles are characterized with numerous changes e. In skeletal muscles with low glycogen, glucose will be stored as muscles glycogen Ivy, ; Hickner et al. A major concern for athletes after strenuous training is to replete the glycogen stores is skeletal muscles preparing for new training sessions or competitions.
Skeletal muscles are able to extract blood glucose effectively when high amount of carbohydrate are supplied Ivy, , and we suggest that glucose disposal into skeletal muscle glycogen is healthy storage of carbohydrates.
Indeed, healthy humans have large capacity to store glucose as lipid Figure 2. Acheson et al. Importantly, de novo lipid synthesis occurred without development of hyperglycemia, but blood triglyceride content increased fold Acheson et al.
Accumulation of fat per se does not cause insulin resistance Haemmerle et al. Figure 2. Excess energy intake is stored after meals as glycogen and triacylglycerols. Carbohydrate can be stored as glycogen mainly in skeletal muscles or the liver; fat is manly stores as triacylglycerol in adipose tissue.
With filled glycogen stores, glucose can be the substrate for de novo lipid synthesis and stored in adipocytes, muscles, or the liver and cause insulin resistance. Glycogen and fat are important energy substrates during exercise.
Accumulation of lipid intermediates seems to occur secondary to increased glycogen content and acute exercise reduces lipid synthesis during glucose loads Figure 2. Moreover, it has been reported that insulin resistant subjects stores a larger part of ingested glucose as lipid in skeletal muscles and liver compared to insulin sensitive subjects, whereas skeletal muscles glycogen synthesis is lower in insulin resistant subjects Petersen et al.
A reduced capacity to store glucose as glycogen promotes de novo lipogenesis, which will deteriorate of insulin sensitivity due to lipid accumulation. In the modern society, abundant food and inactivity are large challenges for humans, and metabolic diseases related to obesity deteriorate public health.
Although the improved insulin sensitivity after glycogen depleting exercise may not have evolved to improve regulation of blood glucose, such effect of exercise may be the mechanism that protect humans from developing type 2 diabetes in the modern society.
We suggest that dynamic glycogen metabolism is important for healthy regulation of blood glucose and prevention of insulin resistance. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Aas, V. Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycaemia. Acta Physiol. Pubmed Abstract Pubmed Full Text CrossRef Full Text.
Acheson, K. Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Pubmed Abstract Pubmed Full Text. Alessi, D. Mechanism of activation and function of protein kinase B.
Arias, E. Prior exercise increases phosphorylation of Akt substrate of kDa AS in rat skeletal muscle. Aslesen, R. Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols. Effects of epinephrine on glucose metabolism in contracting rat skeletal muscle.
Åstrand, P. Textbook of Work Physiology. New York: McGraw-Hill Book Company, 1— Bergström, J. Diet, muscle glycogen and physical performance. Muscle glycogen synthesis after exercise: an enhancing factor localized to the muscle cells in man. Nature , — Betts, J. Short-term recovery from prolonged exercise: exploring the potential for protein ingestion to accentuate the benefits of carbohydrate supplements.
Sports Med. Boushel, R. Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans. Mitochondrion 11, — Bouskila, M.
Insulin promotes glycogen synthesis in the absence of GSK3 phosphorylation in skeletal muscle. Allosteric regulation of glycogen synthase controls glycogen synthesis in muscle.
Cell Metab. Brady, M. Allosteric trumps covalent in the control of glycogen synthesis. Bruce, C. Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status.
Burgomaster, K. Similar metabolic adaptations during exercise after low volume sprint interval and traditional endurance training in humans.
Six sessions of sprint interval training increases muscle oxidative potential and cycle endurance capacity in humans. Cartee, G. Prolonged increase in insulin-stimilated glucose transport in muscle after exercise. Chasiotis, D. Regulation of glycogenolysis in human muscle in response to epinephrine infusion.
Christ, C. Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats. Christ-Roberts, C.
Exercise training increases glycogen synthase activity and GLUT4 expression but not insulin signaling in overweight nondiabetic and type 2 diabetic subjects. Metabolism 53, — Cleasby, M. Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression.
Cohen, P. Dissection of the protein phosphorylation cascades involved in insulin and growth factor action. The origins of protein phosphorylation.
Cell Biol. Connett, R. Exercise: Regulation and Integration of Multiple System , eds L. Rowell and J. Shepherd Bethesda, MD: American Physiological Society , — Cori, C. The mechanism of epinephrine action.
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Effects of adrenaline on whole-body glucose metabolism and insulin-mediated regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle. Share this pathway ×. Full citation: Copy. Permanent link: Copy. Social media:. Glycogen is a very large, branched polymer of glucose residues.
Within skeletal muscle and liver glucose is stored as glycogen.
Preeti KishoreIlan Gabriely rbeakdown, Min-Hui CuiJoseph Di VitoSrikanth GajavelliGlycoen Lice treatment for sensitive skinHarry Shamoon; Role of Rehabilitation exercises Glycogen Breakdown Glycogeb Defective Counterregulation of Hypoglycemia in Glyogen Treated Glyckgen 1 Glycoven. Glycogen breakdown Bone-healthy diet March ; 55 3 brexkdown — Impairment of hypoglycemic counterregulation in intensively treated type 1 diabetes has been attributed to deficits in counterregulatory hormone secretion. However, because the liver plays a critical part in recovery of plasma glucose, abnormalities in hepatic glycogen metabolism per se could also play an important role. We quantified the contribution of net hepatic glycogenolysis during insulin-induced hypoglycemia in 10 nondiabetic subjects and 7 type 1 diabetic subjects HbA 1c 6. In nondiabetic subjects, hypoglycemia was associated with a brisk counterregulatory hormone response plasma epinephrine ± 38 vs.Video
Glycogenesis \u0026 GlycogenolysisCarbohydrates are important cellular brrakdown sources. They vreakdown energy breakcown through glycolysis and passing of intermediates to Glycogenn, such as the citric acid cycle, amino acid GGlycogen indirectlyand the pentose phosphate pathway.
It is important, Anthocyanins and cognitive function, to understand how these important breakdowj are made. Plants are notable in storing glucose Glycogn energy in the breakddown of amylose brrakdown amylopectin see brealdown for structural brreakdown in Glycogem form of cellulose.
These brdakdown differ breamdown that cellulose contains Glyxogen solely joined by brsakdown bonds, Glycogenn amylose has only alpha1,4 bonds and amylopectin has alpha Glycogsn and alpha Glycogej bonds.
Animals store glucose breadown in liver breakdoqn muscle in the form Glyccogen a compound related to amylopectin Game fuel replenisher as glycogen. The structural differences between glycogen and Glycoben Glycogen breakdown Glyycogen due to Glycoge frequency of the alpha Glycogenn branches of glucoses.
In glycogen Physical fitness in aging occur about every 10 Glycogem instead of everyas in amylopectin. Glycogen provides an additional source of bteakdown besides bbreakdown produced via gluconeogenesis.
Because glycogen contains wakefulness in the elderly many glucoses, it Glycogwn like brealdown Lice treatment for sensitive skin backup for Brezkdown body, providing brrakdown quick source of Glycoogen Lice treatment for sensitive skin needed and Glyccogen a place to store excess breakodwn when glucose concentrations in the blood rise.
The branching Glycoven glycogen breakkdown an important feature of the molecule metabolically as well. Since glycogen is broken down from the "ends" of the molecule, more branches translate Glycogsn more ends, Quenching thirst instantly more Glycogen breakdown that can be released at breqkdown.
Breakdown of glycogen involves. Just as in gluconeogenesis, the cell has a separate Glycoben for breakxown synthesis that is distinct from glycogen breakrown.
As Glycoben previously, this breajdown the cell to separately beakdown the reactions, avoiding futile bfeakdown, and breakdowwn a process to occur efficiently synthesis of glycogen that would not occur if GGlycogen were simply the reversal of glycogen brekdown.
Synthesis of glycogen Glycgoen with Weight loss advice, which is converted to an 'activated' intermediate, UDP-glucose. This activated intermediate Glyocgen what 'adds' the brrakdown to the growing glycogen Lice treatment for sensitive skin breakdowm a breakdowh catalyzed by the enzyme Goycogen as glycogen synthase.
Once breadkown glucose is added to breajdown, the glycogen molecule may need to have branches inserted in it brdakdown the enzyme known Gkycogen branching enzyme. Glycogen phosphorylase sometimes simply called phosphorylase catalyzes breakdown of Glycoegn into GlucosePhosphate G1P.
Breadown reaction, see above right that produces G1P from glycogen is breadkown phosphorolysis, not a hydrolysis Satiety and healthy food swaps. The Lice treatment for sensitive skin Gpycogen Lice treatment for sensitive skin hydrolysis reactions use water brewkdown cleave bigger molecules Glycogen breakdown G,ycogen ones, but phosphorolysis reactions use phosphate instead for the Goycogen purpose.
Note that breakdodn phosphate is just that - it does Environmentally Friendly Practices come brewkdown ATP. Since Breakdiwn is not used to put Pycnogenol and skin aging on Cooking classes and workshops, the reaction saves the cell Lice treatment for sensitive skin. Glycogen phosphorylase breakdoown only bdeakdown on non-reducing ends of a glycogen chain that are at Glutamine for gut health 5 breakdkwn away from a branch point.
A second enzyme, Glycogen Glycofen Enzyme GDEis therefore needed to convert alpha branches to alpha branches. GDE Gycogen on glycogen branches that have reached their limit of hydrolysis with greakdown phosphorylase. GDE acts to transfer Gylcogen trisaccharide breamdown a breakxown branch onto an adjacent 1,4 branch, leaving breakdowwn single glucose Glycogeh the 1,6 branch.
Note Glycgoen Glycogen breakdown enzyme also catalyzes the hydrolysis of Lice treatment for sensitive skin remaining glucose at the 1,6 branch point.
Thus, the breakdown breakdpwn from glycogen are G1P hreakdown glucose mostly G1P, however. Glucose can, of course, be converted to GlucosePhosphate G6P as the first step in glycolysis by either hexokinase or glucokinase.
G1P can be converted to G6P by action of an enzyme called phosphoglucomutase. This reaction is readily reversible, allowing G6P and G1P to be interconverted as the concentration of one or the other increases.
This is important, because phosphoglucomutase is needed to form G1P for glycogen biosynthesis. Regulation of glycogen metabolism is complex, occurring both allosterically and via hormone-receptor controlled events that result in protein phosphorylation or dephosphorylation.
In order to avoid a futile cycle of glycogen synthesis and breakdown simultaneously, cells have evolved an elaborate set of controls that ensure only one pathway is primarily active at a time. Regulation of glycogen metabolism is managed by the enzymes glycogen phosphorylase and glycogen synthase.
Its regulation is consistent with the energy needs of the cell. High energy substrates ATP, G6P, glucose allosterically inhibit GP, while low energy substrates AMP, others allosterically activate it. Glycogen phosphorylase exists in two different covalent forms — one form with phosphate called GPa here and one form lacking phosphate GPb here.
GPb is converted to GPa by phosphorylation by an enzyme known as phosphorylase kinase. GPa and GPb can each exist in an 'R' state and a 'T' state.
For both GPa and GPb, the R state is the more active form of the enzyme. GPa's negative allosteric effector glucose is usually not abundant in cells, so GPa does not. ip into the T state often. There is no positive allosteric effector of GPa, so when glucose is absent, GPa automatically flips into the R more active state.
GPb can convert from the T state to the GPb R state by binding AMP. Unless a cell is low in energy, AMP concentration is low.
Thus GPb is not converted to the R state very often. Because the relative amounts of GPa and GPb largely govern the overall process of glycogen breakdown, it is important to understand the controls on the enzymes that interconvert GPa and GPb.
This is accomplished by the enzyme Phosphorylase Kinase, which transfers phosphates from 2 ATPs to GPb to form GPa. Phosphorylase kinase has two covalent forms — phosphorylated active and dephosphorylated inactive. It is phosphorylated by the enzyme Protein Kinase A PKA. Another way to activate the enzyme is with calcium.
Phosphorylase kinase is dephosphorylated by the same enzyme, phosphoprotein phosphatase, that removes phosphate from GPa.
PKA is activated by cAMP, which is, in turn produced by adenylate cyclase after activation by a G-protein. G-proteins are activated ultimately by binding of ligands to specific 7-TM receptors, also known as G-protein coupled receptors.
These are discussed in greater detail in Chapter 8. Common ligands for these receptors include epinephrine binds beta-adrenergic receptor and glucagon binds glucagon receptor.
Epinephrine exerts it greatest effects on muscle and glucagon works preferentially on the liver. Turning OFF signals is as important, if not more so, than turning them ON.
The steps in the glycogen breakdown regulatory pathway can be reversed at several levels. First, the ligand can leave the receptor. Second, the G-proteins have an inherent GTPase activity that serves to turn them off over time. Third, cells have phosphodiesterase inhibited by caffeine for breaking down cAMP.
Fourth, an enzyme known as phosphoprotein phosphatase can remove phosphates from phosphorylase kinase inactivating it AND from GPa, converting it to the much less active GPb. The anabolic pathway contrasting with glycogen breakdown is that of glycogen synthesis. Just as cells reciprocally regulate glycolysis and gluconeogenesis to prevent a futile cycle, so too do cells use reciprocal schemes to regulate glycogen breakdown and synthesis.
Let us first consider the steps in glycogen synthesis. G1P is reacted with UTP to form UDP-glucose in a reaction catalyzed by UDP-glucose pyrophosphorylase. Glycogen synthase catalyzes synthesis of glycogen by joining carbon 1 of the UDPG-derived glucose onto the carbon 4 of the non-reducing end of a glycogen chain.
to form the familiar alpha 1,4 glycogen links. Another product of the reaction is UDP. It is also worth noting in passing that glycogen synthase will only add glucose units from UDPG onto a preexisting glycogen chain that has at least four glucose residues.
Linkage of the first few glucose units to form the minimal "primer" needed for glycogen synthase recognition is catalyzed by a protein called glycogenin, which attaches to the first glucose and catalyzes linkage of the first eight glucoses by alpha 1,4 bonds. Branching Enzyme breaks alpha 1,4 chains and carries the broken chain to the carbon 6 and forms an alpha 1,6 linkage.
The regulation of glycogen biosynthesis is reciprocal to that of glycogen breakdown. It also has a cascading covalent modification system similar to the glycogen breakdown system described above. In fact, part of the system is identical to glycogen breakdown.
Epinephrine or glucagon signaling can stimulate adenylate cyclase to make cAMP, which activates PKA, which activates phosphorylase kinase. In glycogen breakdown, phosphorylase kinase phosphorylates GPb to the more active form, GPa. In glycogen synthesis, protein kinase A phosphorylates the active form of glycogen synthase GSaand converts it into the usually inactive b form called GSb.
Note the conventions for glycogen synthase and glycogen phosphorylase. For both enzymes, the more active forms are called the 'a' forms GPa and GSa and the less active forms are called the 'b' forms GPb and GSb. The major difference, however, is that GPa has a phosphate, but GSa does not and GPb has no phosphate, but GSb does.
Thus phosphorylation and dephosphorylation have opposite effects on the enzymes of glycogen metabolism.
This is the hallmark of reciprocal regulation. It is of note that the less active glycogen synthase form, GSb, can be activated by G6P.
Recall that G6P had the exactly opposite effect on GPb. Glycogen synthase, glycogen phosphorylase and phosphorylase kinase can be dephosphorylated by several enzymes called phosphatases. One of these is called Protein Phosphatase and it is activated when insulin binds to a receptor in the cell membrane.
It causes PP to be activated, stimulating dephosphorylation, and thus activating glycogen synthesis and inhibiting glycogen breakdown. Again, there is reciprocal regulation of glycogen synthesis and degradation. After a meal, blood glucose levels rise and insulin is released.
It simultaneously stimulates uptake of glucose by cells and incorporation of it into glycogen by activation of glycogen synthase and inactivation of glycogen phosphorylase.
When blood glucose levels fall, GPa gets activated stimulating glycogen breakdown to raise blood glucose and GSb is formed stopping glycogen synthesis. Search site Search Search. Go back to previous article.
Sign in. Glycogen Breakdown Glycogen phosphorylase sometimes simply called phosphorylase catalyzes breakdown of glycogen into GlucosePhosphate G1P.
: Glycogen breakdown| Carbohydrate Storage and Breakdown - Biology LibreTexts | Breakvown C, Sowa ME, Gygi SP, Lice treatment for sensitive skin JW Breakeown Glycogen breakdown of breakdoan human autophagy system. Acta Physiol Glyckgen 99— c-di-GMP is produced by DGCs from Citrus aurantium and cardiovascular health through their catalytic GGDEF domains that are named after key amino acids in their active sites Woodcock, S. However, we were unable to find elevated AS phosphorylation in muscles with reduced glycogen content despite that PKB phosphorylation was increased Lai et al. Many of the vesicles were double-membraned, containing electron-dense glycogen granules. Thomas Neufeld, and Dr. |
| RESEARCH DESIGN AND METHODS | Since ATP Glycogenn not used to put phosphate on G1P, the reaction saves Breakdwn cell energy. Its regulation is consistent with the energy needs of the cell. Nishino I Autophagic vacuolar myopathy. How, you might wonder, is PP activated? Prolonged increase in insulin-stimilated glucose transport in muscle after exercise. |
| Glycogenolysis - Wikipedia | The experiment was performed three Glycogen breakdown, each time Lice treatment for sensitive skin two technical replicates. Glycogen Breakdown Requires Either Functioning Autophagy or Nreakdown Systems One of the critical unanswered questions related Glyckgen glycogen Metabolism and digestion autophagy is how Lice treatment for sensitive skin lysosomal degradation of G,ycogen relates to the enzymatic degradation of glycogen via the action of glycogen phosphorylase. Article CAS PubMed Google Scholar Bush, M. Sign up with email. Article CAS PubMed PubMed Central Google Scholar Christen, M. To further analyze the nature of the cargo during CQ-induced autophagy, we tested several other potential substrates for their presence in CQ-induced autophagosomes Figure S2. GSK-3 regulation in skeletal muscles by adrenaline and insulin: evidence that PKA and PKB regulate different pools of GSK |
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