Regulation of rabbit fetal glycogen: effect of in utero fetal decapitation on the metabolism of glycogen in fetal heart, lung, and liver

1986 ◽  
Vol 64 (5) ◽  
pp. 405-412 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
C. Allan Woolever ◽  
Chee Chung Pan
Keyword(s):  
Pyruvate Kinase ◽  
Fetal Heart ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Fetal Lung ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Lactic Dehydrogenase ◽  
In Utero ◽  
Control Mechanisms

To understand the control mechanisms involved in the regulation of fetal glycogen, we have studied the effect of in utero fetal decapitations on glycogen metabolism in rabbit fetal heart, lung, and liver. In utero fetal decapitations were performed between days 18 and 21 of gestation. Two to four fetuses on one side of the horn were decapitated. Fetuses were delivered between days 23 and 26 or between days 28 and 30 of gestation. Fetal heart, lungs, and liver were analyzed for DNA, protein, glycogen, glycogen synthase (I and D forms), glycogen phosphorylase (a and b forms), phosphofructokinase, pyruvate kinase, and lactic dehydrogenase. In fetal heart and lung, no difference was observed in any of the above measurements in the intact and decapitated fetuses. In contrast, fetal liver does not appear to develop the glycogen system as indicated by the very low levels of glycogen (0.02 mg/mg DNA) in decapitated fetuses as compared with intact fetuses (0.4 mg/mg DNA). Similarly the levels of glycogen synthase and phosphorylase were two to three times lower in livers from decapitated fetuses as compared with the livers from intact fetuses. The three enzymes phosphofructokinase, pyruvate kinase, and lactic dehydrogenase were not affected by fetal decapitation in all three tissues. These results indicate that the fetal hypothalamic–pituitary–adrenal (thyroid) axis is not required at least after day 18 of gestation for the normal accumulation and subsequent utilization of glycogen in fetal heart and lungs, while it is an absolute requirement for the development of the fetal liver glycogen system. These results further suggest that maternal and (or) placental hormones may play an important role in the deposition and utilization of fetal lung and heart glycogen.

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.

The variable clinical phenotype of three patients with hepatic glycogen synthase deficiency

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Çiğdem Seher Kasapkara ◽  
Zehra Aycan ◽  
Esma Açoğlu ◽  
Saliha Senel ◽  
Melek Melahat Oguz ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Glucose Monitoring ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Postprandial Hyperglycemia ◽  
Hepatic Glycogen ◽  
Case Presentation ◽  
Ketotic Hypoglycemia ◽  
Fasting Hypoglycemia ◽  
Lactic Acidemia

AbstractBackground:Glycogen synthase deficiency, also known as glycogenosis (GSD) type 0 is an inborn error of glycogen metabolism caused by mutations in theCase presentation:Herein we report three new cases of liver glycogen synthase deficiency (GSD0). The first patient presented at the 4 years of age with recurrent hypoglycemic seizures. The second patient who is the brother of the first patient presented at 15 months with asymptomatic incidental hypoglycemia. Glucose monitoring in both patients revealed daily fluctuations from fasting hypoglycemia to postprandial hyperglycemia and lactic acidemia. A third patient was consulted for ketotic hypoglycemia and postprandial hyperglycemia at the 5 years of age.Conclusions:Genetic analyses of the siblings revealed homozygosity for mutation c.736C>T on the

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

1990 ◽  
Vol 68 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Duncan G. Wallace
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fetal Liver ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Fetal Lung ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Dehydrogenase Complex

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.Key words: glycogen, glycolysis, tricarboxylic acid cycle, pyruvate dehydrogenase, surfactant.

Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis

1976 ◽  
Vol 230 (5) ◽  
pp. 1296-1301 ◽  
Author(s):  
RT Curnow ◽  
EJ Rayfield ◽  
DT George ◽  
TV Zenser ◽  
FR DeRubertis
Keyword(s):  
Cyclic Amp ◽  
Portal Vein ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
In Situ Perfusion ◽  
Glucoregulatory Hormones

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.

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 PSII-39 Trophectoderm-specific RNA interference of chorionic somatomammotropin alters glucose metabolism in sheep fetal liver

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 378-379
Author(s):  
Asghar Ali ◽  
Mary Howerton ◽  
Quinton A Winger ◽  
Paul J Rozance ◽  
Russell V Anthony
Keyword(s):  
Rna Interference ◽  
Glucose Metabolism ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Liver Glycogen ◽  
Immunoblot Analysis ◽  
Maternal Circulation ◽  
Control Shrna ◽  
Chorionic Somatomammotropin ◽  
Receptor Beta

Abstract Chorionic somatomammotropin (CSH) is a placenta-specific hormone and secreted into both fetal and maternal circulation. Reduced maternal CSH is observed with intrauterine growth restriction (IUGR) in both humans and sheep, and it has long been held that CSH modulates maternal and fetal metabolism. We hypothesized that CSH deficiency, created by RNA interference (RNAi), could impact fetal liver glucose metabolism. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 dGA; CSH RNAi pregnancies with IUGR (RNAi-IUGR; n = 8) or without IUGR (RNAi; n = 8). Data from both RNAi phenotypes were compared separately with SC using Welch’s t-test. Liver and placental weights were reduced (P < 0.05) in RNAi-IUGR pregnancies, but not in RNAi pregnancies, as compared to SC (n = 8). Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased (P < 0.05), whereas insulin receptor beta (IRβ) concentration, as determined by Western immunoblot analysis, in fetal liver was increased (P < 0.05) in both RNAi phenotypes. Fetal liver glycogen quantity was also increased (P < 0.05) in both RNAi phenotypes. Glycogen synthase-1 (GYS-1) concentration in fetal liver was increased (P < 0.05) in both RNAi phenotypes, whereas there was no change in GYS-2 concentration. Phosphorylated-GYS (inactive GYS) was reduced (P < 0.05) in fetal livers for both RNAi phenotypes. Lactate dehydrogenase beta (LDHβ) concentration was increased (P < 0.05) and IGF2 concentration was decreased (P < 0.05) in RNAi-IUGR fetal livers only. From these results we conclude that fetal liver glucose metabolism is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced insulin sensitivity in both CSH RNAi phenotypes. Differences between the two phenotypes may help differentiate direct and indirect effects of CSH. Supported by NIH R01 HD093701.

scholarly journals Chorionic somatomammotropin RNA interference alters fetal liver glucose utilization

2020 ◽  
Vol 247 (3) ◽  
pp. 251-262
Author(s):  
Asghar Ali ◽  
Callie M Swanepoel ◽  
Quinton A Winger ◽  
Paul J Rozance ◽  
Russell V Anthony
Keyword(s):  
Glucose Utilization ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Liver Glycogen ◽  
Control Shrna ◽  
Maternal Metabolism ◽  
Igf Binding ◽  
Chorionic Somatomammotropin ◽  
Igf Binding Protein ◽  
Receptor Beta

Chorionic somatomammotropin (CSH) is a placenta-specific hormone associated with fetal growth, and fetal and maternal metabolism in both humans and sheep. We hypothesized that CSH deficiency could impact sheep fetal liver glucose utilization. To generate CSH-deficient pregnancies, day 9 hatched blastocysts were infected with lentiviral particles expressing CSH-specific shRNA (RNAi) or scramble control shRNA (SC) and transferred to synchronized recipients. CSH RNAi generated two distinct phenotypes at 135 days of gestational age (dGA); pregnancies with IUGR (RNAi-IUGR) or with normal fetal weight (RNAi-NW). Fetal body, fetal liver and placental weights were reduced (P < 0.05) only in RNAi-IUGR pregnancies compared to SC. Umbilical artery plasma insulin and insulin-like growth factor 1 (IGF1) concentrations were decreased, whereas insulin receptor beta (INSR) concentration in fetal liver was increased (P < 0.05) in both RNAi phenotypes. The mRNA concentrations of IGF1, IGF2, IGF binding protein 2 (IGFBP2) and IGFBP3 were decreased (P < 0.05) in fetal livers from both RNAi phenotypes. Fetal liver glycogen concentration and glycogen synthase 1 (GYS1) concentration were increased (P < 0.05), whereas fetal liver phosphorylated-GYS (inactive GYS) concentration was reduced (P < 0.05) in both RNAi phenotypes. Lactate dehydrogenase B (LDHB) concentration was increased (P < 0.05) and IGF2 concentration was decreased (P < 0.05) in RNAi-IUGR fetal livers only. Our findings suggest that fetal liver glucose utilization is impacted by CSH RNAi, independent of IUGR, and is likely tied to enhanced fetal liver insulin sensitivity in both RNAi phenotypes. Determining the physiological ramifications of both phenotypes, may help to differentiate direct effect of CSH deficiency or its indirect effect through IUGR.

scholarly journals Altered liver glycogen metabolism in fed genetically obese mice

1983 ◽  
Vol 216 (2) ◽  
pp. 273-280 ◽  
Author(s):  
G van de Werve ◽  
F Assimacopoulos-Jeannet ◽  
B Jeanrenaud
Keyword(s):  
Cyclic Amp ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Liver Glycogen ◽  
Obese Mice ◽  
Apparent Paradox ◽  
Sequential Inactivation ◽  
Altered Liver ◽  
Isolated Liver

The cyclic AMP and glycogen concentrations and the activities of phosphorylase kinase, phosphorylase a and glycogen synthase a were not different in livers from lean or ob/ob mice despite increased plasma glucose and insulin in the obese group. The liver water content was decreased by 10% in the obese mice. In hepatocytes isolated from lean mice and incubated with increasing glucose concentrations (14-112 mM), a sequential inactivation of phosphorylase and activation of glycogen synthase was observed. In hepatocytes from obese mice the inactivation of phosphorylase was not followed by an activation of synthase. The inactivation of phosphorylase occurred more rapidly and was followed by an activation of synthase in hepatocytes isolated from both groups of mice when in the incubation medium Na+ was replaced by K+ or when Ca2+ was omitted and 2.5 mM-EGTA included. The inactivation of phosphorylase and activation of synthase were not different in broken-liver-cell preparations from lean and obese animals. The re-activation of phosphorylase in liver filtrates in the presence of 0.1 microM-cyclic AMP and MgATP was inhibited by about 70% by EGTA and stimulated by Ca2+ and was always greater in preparations from ob/ob mice. The apparent paradox between the impairment of glycogen metabolism in isolated liver preparations and the situation in vivo in obese mice is discussed.

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