Electrical stimulation of the liver cell: activation of glycogenolysis

1981 ◽  
Vol 240 (3) ◽  
pp. E226-E232
Author(s):  
K. A. Freude ◽  
L. S. Sandler ◽  
F. J. Zieve
Keyword(s):  
Electrical Stimulation ◽  
Metabolic Regulation ◽  
Glycogen Phosphorylase ◽  
Cell Activation ◽  
Current Flow ◽  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Liver Glycogen

To examine the role of ionic factors in the regulation of glycogen metabolism, we examined the effects of electrical stimulation on liver glycogen cycle enzymes. Passage of electric current through a suspension of rat hepatocytes caused the conversion of glycogen phosphorylase to its active (a) form and the simultaneous conversion of glycogen synthase to its inactive (D) form. The rise in phosphorylase a activity was dependent on the magnitude of current flow, was detectable after 5 s of current flow, and was rapidly reversible on cessation of stimulation. The activation of phosphorylase by shocking was completely eliminated by depletion of cellular Ca2+ and was restored by readdition of Ca2+. Cyclic AMP and cyclic GMP levels were unaffected by shocking. It is concluded that shocking, in the absence of any hormone or exogenous chemical, causes an increase in cytosol Ca2+, which in turn leads to activation of phosphorylase and inactivation of synthase. Electrical stimulation may serve as a model system for studying the role of ions in metabolic regulation.

scholarly journals Dynamic Variations in Brain Glycogen are Involved in Modulating Isoflurane Anesthesia in Mice

2020 ◽  
Vol 36 (12) ◽  
pp. 1513-1523
Author(s):  
Ze Fan ◽  
Zhihao Zhang ◽  
Shiyi Zhao ◽  
Yuanyuan Zhu ◽  
Dong Guo ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Brain Regions ◽  
Brain Glycogen ◽  
Dynamic Variations ◽  
Term Delivery ◽  
Lower Ratio ◽  
Increased Activity

Abstract General anesthesia severely affects the metabolites in the brain. Glycogen, principally stored in astrocytes and providing the short-term delivery of substrates to neurons, has been implicated as an affected molecule. However, whether glycogen plays a pivotal role in modulating anesthesia–arousal remains unclear. Here, we demonstrated that isoflurane-anesthetized mice exhibited dynamic changes in the glycogen levels in various brain regions. Glycogen synthase (GS) and glycogen phosphorylase (GP), key enzymes of glycogen metabolism, showed increased activity after isoflurane exposure. Upon blocking glycogenolysis with 1,4-dideoxy-1,4-imino-D-arabinitol (DAB), a GP antagonist, we found a prolonged time of emergence from anesthesia and an enhanced δ frequency in the EEG (electroencephalogram). In addition, augmented expression of glycogenolysis genes in glycogen phosphorylase, brain (Pygb) knock-in (PygbH11/H11) mice resulted in delayed induction of anesthesia, a shortened emergence time, and a lower ratio of EEG-δ. Our findings revealed a role of brain glycogen in regulating anesthesia–arousal, providing a potential target for modulating anesthesia.

scholarly journals Fructose-induced increase in intracellular free Mg2+ ion concentration in rat hepatocytes: relation with the enzymes of glycogen metabolism

1997 ◽  
Vol 326 (3) ◽  
pp. 823-827 ◽  
Author(s):  
Vinciane GAUSSIN ◽  
Philippe GAILLY ◽  
Jean-Marie GILLIS ◽  
Louis HUE
Keyword(s):  
Glycogen Phosphorylase ◽  
Time Course ◽  
Buffer Capacity ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Dose Dependence ◽  
Ion Concentration ◽  
Extracellular Medium

In rat hepatocytes subjected to a fructose load, ATP content decreased from 3.8 to 2.6 μmol/g of cells. Under these conditions, the intracellular free Mg2+ ion concentration, as measured with mag-fura 2, increased from 0.25 to 0.43 μmol/g of cells and 0.35 μmol of Mg2+ ions were released per g of cells in the extracellular medium. Therefore the increase in the intracellular free Mg2+ ion concentration was less than expected from the decrease in ATP, indicating that approx. 80% of the Mg2+ ions released from MgATP2- were buffered inside the cells. When this buffer capacity was challenged with an extra Mg2+ ion load by blocking the fructose-induced Mg2+ efflux, again approx. 80% of the extra Mg2+ ion load was buffered. The remaining 20% appearing as free Mg2+ ions in fructose-treated hepatocytes could act as second messenger for enzymes having a Km for Mg2+ in the millimolar range. Fructose activated glycogen synthase and glycogen phosphorylase, although both the time course and the dose-dependence of activation were different. This was reflected in a stimulation of glycogen synthesis with concentrations of fructose below 5 mM. Indeed, activation of glycogen synthase reached a maximum at 30 min of incubation and was observed with small (5 mM or less) concentrations of fructose, whereas the activation of glycogen phosphorylase was almost immediate (within 5 min) and maximal with large doses of fructose. The fructose-induced activation of glycogen phosphorylase, but not that of glycogen synthase, could be related to an increase in free Mg2+ ion concentration.

scholarly journals Altered regulation of glycogen metabolism by vasopressin and phenylephrine in hepatocytes from insulin-resistant obese (fa/fa) rats. Role of protein kinase C

1990 ◽  
Vol 269 (3) ◽  
pp. 795-799 ◽  
Author(s):  
G van de Werve ◽  
D Massillon
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Hormonal Control ◽  
Maximal Response ◽  
Insulin Resistant ◽  
Kinase C

The hormonal control of glycogen synthase and phosphorylase interconversion was investigated in hepatocytes isolated from lean and genetically obese (fa/fa) rats. In cells from obese animals, the inactivation of synthase by 4 β-phorbol 12 β-myristate 13 alpha-acetate (PMA), phospholipase C, vasopressin and the alpha 1-adrenergic agonist phenylephrine was markedly impaired, and the property of PMA to counteract phosphorylase activation by phenylephrine was attenuated. The maximal response of phosphorylase activation to phenylephrine and vasopressin was increased in obese-rat hepatocytes, but the sensitivity to these hormones was similar to that in lean-rat hepatocytes. These observations indicate that the defect in protein kinase C that we reported previously in heart of insulin-resistant fa/fa rats [van de Werve, Zaninetti, Lang, Vallotton & Jeanrenaud (1987) Diabetes 36, 310-319] is probably also expressed in liver.

scholarly journals Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon

1978 ◽  
Vol 176 (3) ◽  
pp. 791-797 ◽  
Author(s):  
Louis Hue ◽  
Juan Emilio Felíu ◽  
Henri-Géry Hers
Keyword(s):  
Protein Kinase ◽  
Pyruvate Kinase ◽  
Incubation Medium ◽  
Glycogen Phosphorylase ◽  
Glycogen Synthase ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Parallel Study ◽  
Isolated Rat Hepatocytes ◽  
Isolated Rat

Hepatocytes isolated from the livers of fed rats were used for a comparative study of the effects of phenylephrine, vasopressin and glucagon on gluconeogenesis and on enzymes of glycogen metabolism. When hepatocytes were incubated in the presence of Ca2+, phenylephrine stimulated gluconeogenesis from pyruvate less than did glucagon, but, in contrast with this hormone, it did not affect the activities of protein kinase and pyruvate kinase, nor the concentration of phosphoenolpyruvate, and it did not decrease the release of 3H2O from [6-3H]glucose. The effects of vasopressin were similar to those of phenylephrine. Gluconeogenesis from fructose was also stimulated by phenylephrine and, more markedly, by glucagon at the expense of the conversion of fructose into lactate. Insulin was able to antagonize the stimulatory effect of phenylephrine on gluconeogenesis from pyruvate. When Ca2+ was removed from the incubation medium, phenylephrine still stimulated gluconeogenesis from pyruvate, but it also caused an activation of protein kinase and an inactivation of pyruvate kinase; accordingly, the concentration of phosphoenolpyruvate was increased, and, in contrast, vasopressin had no effect on all these parameters. The property of phenylephrine to cause the activation of glycogen phosphorylase was decreased by glucose or by the absence of Ca2+; it was abolished when these two conditions were combined. Glycogen synthase was inactivated by phenylephrine in the presence or the absence of Ca2+, although presumably by different mechanisms.

scholarly journals Effects of C-1-substituted glucose analogue on the activation states of glycogen synthase and glycogen phosphorylase in rat hepatocytes

1995 ◽  
Vol 311 (3) ◽  
pp. 845-852 ◽  
Author(s):  
M Board ◽  
M Bollen ◽  
W Stalmans ◽  
Y Kim ◽  
G W J Fleet ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Kinase Inhibitor ◽  
Glycogen Synthase ◽  
Kinetic Studies ◽  
Rat Hepatocytes ◽  
Glycogen Metabolism ◽  
Isolated Hepatocytes ◽  
Effective Control ◽  
Subsequent Addition ◽  
Glucose Analogue

A series of glucose-analogue inhibitors of glycogen phosphorylase b (GPb) has been designed, synthesized and investigated in crystallographic binding and kinetic studies. The aim is to produce a compound that may exert more effective control over glycogen metabolism than the parent glucose molecule and which could alleviate hyperglycaemia in Type-II diabetes. N-Acetyl-beta-D-glucopyranosylamine (1-GlcNAc) has a Ki for muscle GPb in crude extracts of 30 microM, 367-fold lower than that of beta-D-glucose [Board, Hadwen and Johnson (1995) Eur. J. Biochem. 228, 753-761]. In the current work, the effects of 1-GlcNAc on the activation states of GP and glycogen synthase (GS) in cell-free preparations and in isolated hepatocytes are reported. In gel-filtered extracts of liver, which lack ATP for kinase activity, 1-GlcNAc produced a rapid and time-dependent inactivation of GP with a subsequent activation of GS. Effects of 1-GlcNAc on both enzymes were stronger than those of glucose, with 0.8 mM 1-GlcNAc being equipotent with 50 mM glucose. At 1 mM, 1-GlcNAc enhanced the dephosphorylation of exogenous GPa by liver extracts (600%) and by muscle extracts (75%). This represents an approximately 500-fold improvement on glucose for the liver activity and 40-fold for the muscle activity. In whole hepatocytes, 1-GlcNAc showed an approximately 5-fold enhancement of glucose effects for GP inactivation but failed to elicit activation of GS. Glucose-induced activation of GS in whole hepatocytes was reversed by subsequent addition of 1-GlcNAc. However, when GS activation was achieved via the adenosine analogue and kinase inhibitor, 5′-iodotubercidin (ITU), subsequent addition of 1-GlcNAc allowed continued activation of GS. Phosphorylation of 1-GlcNAc in rat hepatocytes was established using radiolabelled material. The rate of phosphorylation was 1.60 nmol/min per 10(6) cells at 20 mM 1-GlcNAc but was reduced by the presence of 50 microM ITU (0.775 nmol/min per 10(6) cells). It is suggested that the phosphorylated derivative of 1-GlcNAc formed in hepatocytes is 1-GlcNAc 6-phosphate and that the presence of this species is responsible for the failure of 1-GlcNAc to activate GS. The relative importance of the reduction in concentration of GPa versus increased glucose 6-phosphate levels for activation of GS is discussed.

Role of glucocorticoid in the regulation of glycogen metabolism in skeletal muscle

1991 ◽  
Vol 260 (6) ◽  
pp. E927-E932 ◽  
Author(s):  
L. Coderre ◽  
A. K. Srivastava ◽  
J. L. Chiasson
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Glycogen Phosphorylase ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Activity Ratios ◽  
Resting Muscle ◽  
Glycogen Breakdown

With the use of the hindlimb perfusion technique, the effect of glucocorticoid on the regulation of glycogen metabolism was studied in rat skeletal muscle. Rats were adrenalectomized (ADX) or sham operated (controls) 14 days before the study. The ADX animals were treated with either saline or corticosterone, and the hindlimbs were perfused at rest or during muscle contraction with saline or epinephrine (10(-7) M). In the resting state, the glycogen content was 33.0 +/- 1.9 mumol/g in the controls, and the activity ratios of glycogen phosphorylase (GPase) and glycogen synthase (GSase) were 0.27 +/- 0.03 and 0.15 +/- 0.02, respectively. Epinephrine treatment increased GPase activity (0.78 +/- 0.03) and decreased GSase activity (0.05 +/- 0.01), which resulted in decreased glycogen content (25.7 +/- 0.9 mumol/g; P less than 0.01). Adrenalectomy induced a 35% reduction in glycogen content but had no effect on the activities of basal enzymes. Under these conditions, however, epinephrine had no effect on GPase activity, had a diminished effect on GSase activity (0.11 +/- 0.01), and did not induce further glycogen breakdown. Corticosterone replacement normalized muscle glycogen content in ADX rats as well as the response of the enzymes to epinephrine. Muscle contraction resulted in a decrease in glycogen content (8.9 +/- 1.3 mumol/g) and in GPase activity (0.14 +/- 0.02) and an increase in GSase activity (0.25 +/- 0.01); this was not affected by adrenalectomy nor by epinephrine. In conclusion, these data indicate that glucocorticoid is essential for the effects of epinephrine on GPase activation. on GSase inhibition, and consequently on glycogen breakdown in resting muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Heterologous desensitization of the cyclic AMP-independent glycogenolytic response in rat liver cells

1981 ◽  
Vol 200 (3) ◽  
pp. 509-514 ◽  
Author(s):  
B Bréant ◽  
S Keppens ◽  
H De Wulf
Keyword(s):  
Cyclic Amp ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Receptor Interaction ◽  
Alpha Adrenergic Receptors ◽  
Rat Liver Cells ◽  
Heterologous Desensitization ◽  
Highly Correlated ◽  
Alpha Agonist

Vasopressin and alpha-adrenergic agonists are known to be potent cyclic AMP-independent Ca2+-dependent activators of liver glycogen phosphorylase. When hepatocytes are pre-incubated with increasing concentrations of vasopressin or of the alpha-agonist phenylephrine, they become progressively unresponsive to a second addition of the respective agonist. The relative abilities of six vasopressin analogues and of five alpha-agonists to activate glycogen phosphorylase and to cause subsequent desensitization are highly correlated, indicating that the same vasopressin and alpha-adrenergic receptors are involved in both responses. About 5-times-higher peptide concentrations are needed to desensitize the cells than to activate their glycogen phosphorylase, whereas the concentrations of alpha-agonists required for the desensitization are only twice those needed for the activation of phosphorylase. The desensitization is not mediated by a perturbation in the agonist-receptor interaction. It is clearly heterologous, i.e. it is not agonist-specific, and must therefore involve a mechanism common to both series of agonists. The evidence for a role of Ca2+ movements or phosphatidylinositol turnover is briefly discussed.

Ontogeny of some enzymes of glycogen metabolism in rabbit fetal heart, lungs, and liver

1983 ◽  
Vol 61 (4) ◽  
pp. 191-197 ◽  
Author(s):  
Bhagu R. Bhavnani
Keyword(s):  
Glycogen Phosphorylase ◽  
Fetal Heart ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Active Form ◽  
Fetal Lung ◽  
Glycogen Metabolism ◽  
Near Term ◽  
Surfactant Phospholipids ◽  
Total Tissue

Optimum conditions were established for the assay of glycogen, glycogen synthase, glycogen phosphorylase, phosphoglucomutase, and glucose-6-phosphatase in rabbit fetal heart, lung, and liver. Using these methods, the pattern of appearance of glycogen and the above four enzymes was established from day 18 of gestation to day 8 after birth. The results indicate that total tissue glycogen reaches maximum levels between days 22 and 24 in the heart, days 24 and 26 in the lung, and days 30 and 31 in the liver. In all three tissues, the rapid rise or depletion of glycogen is coincident with a corresponding increase in glycogen synthase and glycogen phosphorylase activities. However, substantial amounts of glycogen synthase are present both prior to and after the accumulation of glycogen. Similarly, considerable amounts of glycogen phosphorylase are present early in gestation, yet deposition of glycogen occurs. Both the I and D forms of glycogen synthase are present in the three tissues, the major being the physiologically inactive D form. Similarly both the a and b forms of glycogen phosphorylase are present, with the a form (active form) making up about 30–60% of the total phosphorylase activity. Glucose-6-phosphatase was absent in fetal heart and lung throughout the period of gestation investigated. Low levels of this enzyme were detectable in fetal liver near term. The phosphoglucomutase activity increased progressively from day 22 of gestation in all three tissues and continues to increase after birth. The disappearance of fetal lung glycogen occurs between days 27 and 28 at a time when surfactant phospholipids first appear. These findings indicate that the breakdown of glycogen is providing the fetal lung cells with energy necessary for surfactant phospholipid biosynthesis.

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