The role of glycogen synthase phosphatase in the glucocorticoid-induced deposition of glycogen in foetal rat liver

1. The mechanism that underlies the induction of glycogen synthesis in the foetal rat liver by glucocorticoids was reinvestigated in conditions where the accumulation of glycogen is either precociously induced with dexamethasone or inhibited by steroid deprivation. It appears that glucocorticoids act as the physiological trigger for glycogen synthesis by inducing both glycogen synthase (a known effect) and its activating enzyme, glycogen synthase phosphatase. 2. The activity of glycogen synthase phosphatase in adult liver stems from the interaction of two protein components [Doperé, Vanstapel & Stalmans (1980) Eur. J. Biochem. 104, 137–146]. Two independent experimental approaches indicate that the cytosolic ‘S-component’ is already well developed in the foetal liver before the onset of glycogen synthesis. The manifold glucocorticoid-dependent increase in synthase phosphatase activity during late gestation must be attributed to the specific development of the glycogen-bound ‘G-component’.

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Development of adenylate kinase isoenzymes in rat liver

Biochemical Journal ◽

10.1042/bj1220553 ◽

1971 ◽

Vol 122 (4) ◽

pp. 553-555 ◽

Cited By ~ 6

Author(s):

R. Filler ◽

W. E. Criss

Keyword(s):

Rat Liver ◽

Liver Cell ◽

Adenylate Kinase ◽

Energy Flow ◽

Kinase Activity ◽

Adult Liver ◽

Foetal Liver ◽

Foetal Rat ◽

Wet Weight ◽

Developing Rat

Total adenylate kinase activity was determined in developing rat liver. The activity was 18 units/g wet weight of tissue in foetal liver; this increased to 41 units/g immediately after birth and continued increasing until adult activities of 150 units/g were reached after two weeks. The adenylate kinase activity was separated into four isoenzymes. Only isoenzymes II and III were observed in foetal rat liver. Isoenzyme II activity was 2 units/g in the foetal liver and increased to 25 units/g in adult liver. Adenylate kinase III activity was 20 units/g in the foetal liver and increased to 118 units/g in adult liver. The possible role that adenylate kinase might have in regulating the energy flow in the developing liver cell is discussed.

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The role of prolactin and progesterone in the regulation of lipogenesis in maternal and foetal rat liver in vivo and in isolated hepatocytes during the last day of gestation

Biochemical Journal ◽

10.1042/bj2390135 ◽

1986 ◽

Vol 239 (1) ◽

pp. 135-139 ◽

Cited By ~ 30

Author(s):

M Lorenzo ◽

C Roncero ◽

M Benito

Keyword(s):

Rat Liver ◽

Lipid Synthesis ◽

Isolated Hepatocytes ◽

Hepatic Lipogenesis ◽

Treatment Conditions ◽

Foetal Liver ◽

Foetal Rat

The administration of progesterone on day 21 of gestation increases the rates of lipogenesis in the liver in vivo and in hepatocytes isolated from rats on day 22 of pregnancy. Bromocriptine administration increases the rates of hepatic lipogenesis in vivo, but has no effect on lipid synthesis in hepatocytes under the same treatment conditions. Concurrently, the administration of progesterone or bromocriptine on day 21 to the mother increases the rates of lipogenesis in the foetal liver in vivo on day 22. The rates of lipid synthesis in foetal isolated hepatocytes are increased by progesterone administration, but remain unchanged by bromocriptine.

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Multiple metabolic effects of CGRP in conscious rats: role of glycogen synthase and phosphorylase

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.1.e1 ◽

1993 ◽

Vol 264 (1) ◽

pp. E1-E10 ◽

Cited By ~ 2

Author(s):

L. Rossetti ◽

S. Farrace ◽

S. B. Choi ◽

A. Giaccari ◽

L. Sloan ◽

...

Keyword(s):

Skeletal Muscle ◽

Glycogen Synthase ◽

Hepatic Glucose Production ◽

Glycogen Synthesis ◽

Plasma Concentrations ◽

Glucose Production ◽

Glucose Disposal ◽

Hepatic Glucose ◽

Intracellular Glucose

Calcitonin gene-related peptide (CGRP) is a neuropeptide that is released at the neuromuscular junction in response to nerve excitation. To examine the relationship between plasma CGRP concentration and intracellular glucose metabolism in conscious rats, we performed insulin (22 pmol.kg-1.min-1) clamp studies combined with the infusion of 0, 20, 50, 100, 200, and 500 pmol.kg-1.min-1 CGRP (plasma concentrations ranging from 2 x 10(-11) to 5 x 10(-9) M). CGRP antagonized insulin's suppression of hepatic glucose production at plasma concentrations (approximately 10(-10) M) that are only two- to fivefold its basal portal concentration. Insulin-mediated glucose disposal was decreased by 20-32% when CGRP was infused at 50 pmol.kg-1.min-1 (plasma concentration 3 x 10(-10) M) or more. The impairment in insulin-stimulated glycogen synthesis in skeletal muscle accounted for all of the CGRP-induced decrease in glucose disposal, while whole body glycolysis was increased despite the reduction in total glucose uptake. The muscle glucose 6-phosphate concentration progressively increased during the CGRP infusions. CGRP inhibited insulin-stimulated glycogen synthase in skeletal muscle with a 50% effective dose of 1.9 +/- 0.36 x 10(-10) M. This effect on glycogen synthase was due to a reduction in enzyme affinity for UDP-glucose, with no changes in the maximal velocity. In vitro CGRP stimulated both hepatic and skeletal muscle adenylate cyclase in a dose-dependent manner. These data suggest that 1) CGRP is a potent antagonist of insulin at the level of muscle glycogen synthesis and hepatic glucose production; 2) inhibition of glycogen synthase is its major biochemical action in skeletal muscle; and 3) these effects are present at concentrations of the peptide that may be in the physiological range for portal vein and skeletal muscle. These data underscore the potential role of CGRP in the physiological modulation of intracellular glucose metabolism.

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The development of gluconeogenesis in rat liver. Effects of glucagon and ether

Biochemical Journal ◽

10.1042/bj1200385 ◽

1970 ◽

Vol 120 (2) ◽

pp. 385-392 ◽

Cited By ~ 22

Author(s):

Helen Philippidis ◽

F. J. Ballard

Keyword(s):

Rat Liver ◽

Redox State ◽

Phosphoenolpyruvate Carboxykinase ◽

Fold Increase ◽

Similar Increase ◽

Ether Anaesthesia ◽

Foetal Liver ◽

Foetal Rat ◽

Newborn Animals

1. Administration of glucagon to foetal rats produced a 10–15-fold increase in hepatic phosphoenolpyruvate carboxykinase activity together with a similar increase in the overall pathway of pyruvate conversion into glycogen in liver slices. 2. Glucagon was without effect on gluconeogenesis in vivo, which remained at approx. 0.1% of the incorporation as measured in newborn animals. 3. The apparent discrepancy between these results was due to the ether anaesthesia that was required for experimentation in vivo. Under conditions when minimal ether was used, the rates of labelling of glycogen from [3-14C]pyruvate in vivo were increased 10–20-fold and there was an additional stimulus by glucagon. 4. Ether anaesthesia produced a more reduced redox state of the foetal liver cytosol and lowered the ATP/ADP concentration ratio. 5. It is proposed that these effects are significant in the limitation of gluconeogenesis in the foetal rat liver, so that only with high phosphoenolpyruvate carboxykinase activity, high ATP concentration and a relatively oxidized cytosol redox state will a functional gluconeogenic pathway be present.

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Stimulating role of potassium ions and ouabain on glycogen synthesis in adipose tissue

Biochemical Journal ◽

10.1042/bj2080261 ◽

1982 ◽

Vol 208 (2) ◽

pp. 261-268 ◽

Cited By ~ 3

Author(s):

F Sobrino ◽

G Ruiz ◽

R Goberna

Keyword(s):

Adipose Tissue ◽

Glucose Oxidation ◽

Glycogen Synthase ◽

Glycogen Synthesis ◽

Active Form ◽

Potassium Ions ◽

Primary Determinant ◽

Molecular Mechanism Of Action ◽

Fat Pads

1. Exposure of fat-pads to increasing concentrations of K+ in the presence of insulin stimulates the incorporation of labelled glucose into glycogen. In the absence of hormone, only a slight incorporation of glucose into glycogen and slight glucose oxidation were detectable. 2. Ouabain alone, up to 100 microM, had no effect on synthesis of glycogen. Ouabain reinforced the effect of insulin on the conversion of glucose into glycogen in a Na+ medium and in a equimolar Na+-K+ medium, but not in a K+ medium. In addition, ouabain modified the optimal K+/Na+ ratio for glycogen synthesis. 3. The proportion of glycogen synthase in the active form was increased in a K+ medium, and a faster rate of conversion of synthase b into a was observed under these conditions. No difference was detected in the rate of inactivation of phosphorylase in a K+ or a Na+ medium. 4. Even though these results, taken together, are consistent with the proposed role of phosphorylase a in the regulation of synthase activation, the molecular mechanism of action of K+ in adipose tissue in increasing synthesis of glycogen cannot be explained simply by a faster inactivation of phosphorylase a. It is concluded that some undetermined effector(s) or signal could itself be a primary determinant for the greater activation of synthase observed in a K+ medium.

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Role of the direct and indirect pathways for glycogen synthesis in rat liver in the postprandial state.

Journal of Clinical Investigation ◽

10.1172/jci113397 ◽

1988 ◽

Vol 81 (3) ◽

pp. 872-878 ◽

Cited By ~ 35

Author(s):

M T Huang ◽

R L Veech

Keyword(s):

Rat Liver ◽

Glycogen Synthesis ◽

Postprandial State

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Heating after intense repeated contractions inhibits glycogen accumulation in mouse EDL muscle: role of phosphorylase in postexercise glycogen metabolism

AJP Cell Physiology ◽

10.1152/ajpcell.00315.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. C706-C713 ◽

Cited By ~ 1

Author(s):

Sarah J. Blackwood ◽

Ester Hanya ◽

Abram Katz

Keyword(s):

Glycogen Synthase ◽

Glycogen Synthesis ◽

Glycogen Metabolism ◽

Type Ii ◽

Muscle Type ◽

Phosphorylase Activity ◽

Glycogen Accumulation ◽

Longus Muscle ◽

Edl Muscle

The effects of heating on glycogen synthesis (incorporation of [14C]glucose into glycogen) and accumulation after intense repeated contractions were investigated. Isolated mouse extensor digitorum longus muscle (type II) was stimulated electrically to perform intense tetanic contractions at 25°C. After 120 min recovery at 25°C, glycogen accumulated to almost 80% of basal, whereas after recovery at 35°C, glycogen remained low (~25% of basal). Glycogen synthesis averaged 0.97 ± 0.07 µmol·30 min−1·g wet wt−1 during recovery at 25°C and 1.48 ± 0.08 during recovery at 35°C ( P < 0.001). There were no differences in phosphorylase and glycogen synthase total activities nor in phosphorylase fractional activity, whereas glycogen synthase fractional activity was increased by ~50% after recovery at 35°C vs. 25°C. Inorganic phosphate (Pi, substrate for phosphorylase) was markedly increased (~300% of basal) following contraction but returned to control levels after 120 min recovery at 25°C. In contrast, Pi remained elevated after recovery at 35°C (>2-fold higher than recovery at 25°C). Estimates of glycogen breakdown indicated that phosphorylase activity (either via inhibition at 25°C or activation at 35°C) was responsible for ~60% of glycogen accumulation during recovery at 25°C and ~45% during recovery at 35°C. These data demonstrate that despite the enhancing effect of heating on glycogen synthesis during recovery from intense contractions, glycogen accumulation is inhibited owing to Pi-mediated activation of phosphorylase. Thus phosphorylase can play a quantitatively important role in glycogen biogenesis during recovery from repeated contractions in isolated type II muscle.

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Relationship between lipogenesis and glycogen synthesis in maternal and foetal tissues during late gestation in the rat. Effect of dexamethasone

Biochemical Journal ◽

10.1042/bj2040865 ◽

1982 ◽

Vol 204 (3) ◽

pp. 865-868 ◽

Cited By ~ 7

Author(s):

M Benito ◽

M Lorenzo ◽

J M Medina

Keyword(s):

Fatty Acid ◽

Plasma Glucose ◽

Inverse Relationship ◽

Glycogen Synthesis ◽

Lipid Synthesis ◽

Blood Lipid ◽

Late Gestation ◽

Foetal Liver ◽

Foetal Lung

Treatment with dexamethasone enhanced 3H2O incorporation into liver and blood lipid, and also increased plasma glucose, insulin, non-esterified fatty acid and triacylglycerol concentrations during late gestation in the mother rat. An inverse relationship between glycogen and lipid synthesis in foetal liver and lung was observed in control rats. This relationship was also observed in foetal liver, but not in foetal lung, after treatment with dexamethasone.

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