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.

The role of insulin in the synthesis of fetal glycogen

1969 ◽  
Vol 47 (11) ◽  
pp. 917-921 ◽  
Author(s):  
J. G. Manns ◽  
R. P. Brockman
Keyword(s):  
Muscle Glycogen ◽  
Fetal Liver ◽  
Liver Glycogen ◽  
Insulin Antibodies ◽  
Insulin Antibody ◽  
Regulatory Effect ◽  
Maternal Circulation ◽  
Rat Fetuses ◽  
Unanesthetized Animals

Experiments were performed on 21-day-old rat fetuses to determine the effect of insulin or insulin antibodies on the incorporation of 14C-glucose into liver and muscle glycogen. Radioactive glucose was infused for 4 h into the maternal circulation; experiments were done on unanesthetized animals. Fetuses injected with insulin incorporated more 14C-glucose into liver glycogen than littermate controls; fetuses injected with insulin antibody incorporated less than their controls. The results suggest that insulin has a regulatory effect on the synthesis of fetal liver glycogen.

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.

Case Report: Liver Glycogen Synthase Deficiency A Cause of Ketotic Hypoglycemia

PEDIATRICS ◽  
2001 ◽  
Vol 108 (2) ◽  
pp. 495-497 ◽  
Author(s):  
S. L. Rutledge ◽  
J. Atchison ◽  
N. U. Bosshard ◽  
B. Steinmann
Keyword(s):  
Case Report ◽  
Glycogen Synthase ◽  
Liver Glycogen ◽  
Ketotic Hypoglycemia

The Protective Efficacy of Ethanolic Leaves Extract of Citronella Gras (Cymbopogon nardus) on Glucose Metabolism Alteration Induced By Mercury in Rats

2017 ◽  
Vol 9 (03) ◽  
Author(s):  
Fransisca Diana Alexandra ◽  
Dian Mutiasari ◽  
Trilianty Lestarisa ◽  
Eko Suhartono
Keyword(s):  
Glucose Metabolism ◽  
Protective Effect ◽  
Plant Extract ◽  
Protective Efficacy ◽  
Liver Weight ◽  
Liver Glycogen ◽  
Liver Cells ◽  
Glycogen Level ◽  
Group I ◽  
Citronella Grass

The present study was undertaken to investigate the protective effect of ethanolic citronella grass (C. nardus) leaves extract against mercury (Hg) induced glucose metabolism alteration in rats. Four groups of rats were selected, with 6 rats for each group. Animals of group I was received a 1 ppm of Hg only. Animals of groups II, III, and IV received a combination of 1 ppm Hg and plant extract in different dose (1650, 2520, and 3360 mg/ml). The experiment lasted for 4 weeks. The various parameters studied included liver weight, liver glucose, glycogen, and malondialdehyde (MDA) level in all groups after treatment. The results of this present studies showed that the Hg-induced glucose metabolism alteration in rats which can be seen from the increase of liver glucose and the decreasing of liver glycogen levels. The results also showed that the Hginduced glucose metabolism alteration through its activities in the trigger the liver cells damage which can be seen from the decreasing of liver weight and the increase of liver MDA level. The ethanolic of C. nardus leaves extract shows a protective effect to maintain all parameters into a better a condition which can be seen from the significant increase in liver weight and liver glycogen level, and the significant decrease in liver glucose and MDA levels. The present study indicated that the ethanolic C. nardus leaves extract showed a potential protective effect on glucose metabolism alteration induced by Hg

scholarly journals 152 Impact of chorionic somatomammotropin RNA interference on uterine blood flow and placental glucose uptake in the absence of intrauterine growth restriction

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 121-121
Author(s):  
Amelia R Tanner ◽  
Asghar Ali ◽  
Quinton A Winger ◽  
Paul J Rozance ◽  
Russell V Anthony
Keyword(s):  
Rna Interference ◽  
Glucose Uptake ◽  
Intrauterine Growth Restriction ◽  
Growth Restriction ◽  
Intrauterine Growth ◽  
Blood Flows ◽  
Umbilical Blood ◽  
Exact Function ◽  
Chorionic Somatomammotropin ◽  
The Impact

Abstract Chorionic somatomammotropin (CSH) is one of the most abundant hormones produced by the sheep placenta, yet the exact function of CSH has been elusive. Previously we reported the use of in vivo RNA interference (RNAi) to assess the impact of CSH deficiency on placental and fetal growth in sheep. Near-term (135 dGA), there are two distinct CSH RNAi phenotypes: 1) pregnancies with intrauterine growth restriction (IUGR), and 2) pregnancies with normal fetal and placental weights. This study describes physiological changes in the latter phenotype. To generate the CSH RNAi pregnancies, the trophectoderm of hatched blastocysts (9 dGA) were infected with lentiviral-constructs expressing either a scrambled control (NTS) or CSH-specific shRNA (CSH RNAi), prior to transfer into synchronized recipient ewes. At 120 dGA, 6 NTS and 6 CSH RNAi pregnancies were fitted with maternal and fetal catheters. Uterine and umbilical blood flows were measured utilizing the 3H2O transplacental diffusion technique at 132 dGA, and nutrient uptakes were calculated by the Fick principle. Resulting data were analyzed by Student’s t-test and significance was set at P ≤ 0.05. CSH RNAi tended (P ≤ 0.10) to reduce placentome weight with no effect on fetal weight. Absolute (ml/min) and relative (ml/min/kg fetus) uterine blood flows were reduced (P ≤ 0.05) in CSH RNAi pregnancies, but umbilical flows were not impacted. The uterine artery-to-vein glucose gradient (mmol/l) was significantly (P ≤ 0.05) increased, whereas the gradients for taurine and glycine were reduced (P ≤ 0.05). Uteroplacental glucose uptake (mmol/min/kg placenta) was increased 27% (P ≤ 0.05), whereas umbilical glucose uptake (mmol/min/kg fetus) was reduced 13%. This cohort demonstrates that even in the absence of IUGR, CSH deficiency has significant physiological ramifications, and the investigation of CSH RNAi pregnancies exhibiting both IUGR and non-IUGR phenotypes may help determine the direct effects of CSH and its potential impact on fetal programming. Supported by NIH R01 HD093701.

scholarly journals Mechanism of activation of liver glycogen synthase by swelling.

1992 ◽  
Vol 267 (9) ◽  
pp. 5823-5828
Author(s):  
A.J. Meijer ◽  
A Baquet ◽  
L Gustafson ◽  
G.M. van Woerkom ◽  
L Hue
Keyword(s):  
Glycogen Synthase ◽  
Liver Glycogen

Metabolic effects of oral fructose in the liver of fasted rats

1984 ◽  
Vol 247 (4) ◽  
pp. E505-E512 ◽  
Author(s):  
C. B. Niewoehner ◽  
D. P. Gilboe ◽  
G. A. Nuttall ◽  
F. Q. Nuttall
Keyword(s):  
Uric Acid ◽  
Portal Vein ◽  
Hepatic Vein ◽  
Glycogen Synthase ◽  
Control Level ◽  
Liver Glycogen ◽  
Glycogen Storage ◽  
Metabolic Effects ◽  
Serum Triglycerides ◽  
Fasted Rats

Twenty-four-hour-fasted rats were given fructose (4 g/kg) by gavage. Fructose absorption and the portal vein, aorta, and hepatic vein plasma fructose, glucose, lactate, and insulin concentrations as well as liver fructose and fructose 1-P, glucose, glucose 6-P, UDPglucose, lactate, pyruvate, ATP, ADP, AMP, inorganic phosphate (Pi), cAMP, and Mg2+, and glycogen synthase I and phosphorylase alpha were measured at 10, 20, 30, 40, 60 and 120 min after gavage. Liver and muscle glycogen and serum uric acid and triglycerides also were measured. Fifty-nine percent of the fructose was absorbed in 2 h. There were modest increases in plasma and hepatic fructose, glucose, and lactate and in plasma insulin. Concentrations in the portal vein, aorta, and hepatic vein plasma indicate rapid removal of fructose and lactate by the liver and a modest increase in production of glucose. The source of the increase in plasma lactate is uncertain. Hepatic glucose 6-P increased twofold; UDPglucose rose transiently and then decreased below the control level. Fructose 1-P increased linearly to a concentration of 3.3 mumol/g wet wt by 120 min. There was no change in ATP, ADP, AMP, cAMP, Pi, or Mg2+. Serum triglycerides and uric acid were unchanged. Glycogen synthase was activated by 20 min without a change in phosphorylase alpha. This occurred with a fructose dose that did not significantly increase either the liver glucose or fructose concentrations. Liver glycogen increased linearly after 20 min, and glycogen storage was equal in liver (38.4%) and muscle (36.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

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