Hormonal Regulation of Glycogen Metabolism in Human Fetal Liver: I. Normal Development and Effects of Dibutyryl Cyclic AMP, Glucagon, and Insulin in Liver Explants

Schwartz, Alan L.; Räihä, Niels C. R.; Rall, T. W.

doi:10.2337/diab.24.12.1101

Cited by 16 publications

(10 citation statements)

References 14 publications

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“…Hepatic glycogen deposits accumulate during fetal life, indicating that the ontogenic regulation of the activities of glycogen phosphorylase and glycogen synthase favors glycogen biosynthesis (10). However, we report that infusion of ritodrine into fetal lambs between 128 and 135 days gestation results in depletion of hepatic glycogen to levels similar to those seen below 125 days gestation.…”

Section: Discussionmentioning

confidence: 50%

“…The increased activities of glycogen phosphorylase kinase and of glycogen phosphorylase a in fetal liver homogenates suggest that known /3-adrenergic agonist pathways involving phosphorylation of glycogen phosphorylase were responsible for the depletion of hepatic glycogen (7,10). However, glycogen synthase activity was unchanged after 0-2 agonist stimulation.…”

Section: Discussionmentioning

confidence: 93%

“…Glycogen phosphorylase (EC 2.4.1. l) activity of tissue homogenate was assayed by measuring the rate of NADPH generation using the method of Schwartz et al (10). Glycogen content was analyzed by the method of Lowry and Passoneau (1 l) in which NADPH generation from glucose-6-phosphate is measured fluorimetrically.…”

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confidence: 99%

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Effects of β-2 Agonist on Hepatic Glycogen Metabolism in the Fetal Lamb

et al. 1988

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ABSTRACT. To determine the effects of fetal 8-2 agonist fetal lambs results in increased serum glucose levels with elevaexposure on fetal hepatic glycogen metabolism, we infused tion of serum lactate and pyruvate concentrations, and attributed ritodrine at a rate of 1.3 f 0.4 pg/kg/min (mean f SD) for these effects to increased glycolysis. 24 h into six chronically catheterized twin fetal lambs Hepatic glycogen deposition and mobilization are regulated starting between 128 and 134 days gestation. The control by the relative activities of glycogen synthase and glycogen twins received 0.9% saline at 1.2 f 0.12 mllkglh. In phosphorylase, which are in turn regulated by phosphorylase addition, 15 uncatheterized fetuses were killed between kinase and protein phosphatase-1 (7). Phosphorylation of glyco-115 and 148 days gestation as unoperated controls. Rito-gen phosphorylase by phosphorylase kinase activates glycogen drine infusion produced a 1.7-fold elevation in fetal serum phosphorylase, thereby increasing the rate of biodegradation of glucose level, from 23 f 5 to 42 f 15 mgldl, and a 2-fold glycogen. In contrast, phosphorylation of glycogen synthase by elevation in serum insulin level, from 16 f 5 to 34 f 8 mg/ phosphorylase kinase deactivates glycogen synthase, thereby deml, p < 0.01. Hepatic glycogen content increased 7-fold in creasing the rate of glycogen biosynthesis. Protein phosphatasethe uncatheterized controls between 115 and 148 days 1 dephosphorylates glycogen phosphorylase and glycogen syngestation (r = 0.9, p < 0.001). Ritodrine infusion reduced thase, respectively, decreasing and increasing enzyme activity.hepatic glycogen content by 50% from 179 f 19 pglmg inThe purpose of our study was to determine the effects of fetal twin controls to 90 f 25 pglmg in the ritodrine-infused ritodrine exposure on hepatic glycogen metabolism. twins, p < 0.001. Hepatic glycogen phosphorylase kinase activity was elevated 1.3-fold from 0.149 + 0.100 mU/mg protein in control twins to 0.186 f 0.007 mU/mg protein MATERIALS AND METHODS in the ritodrine infused twins, P < 0.001. Glycogen ~h o s -Animalpreparation. Between 120 and 124 days gestation (term ~h o r~l a s e a activity was also increased 1.4-fold from 8-60 is 148 days), six time-dated pregnant ewes were operated on 0.76 nM NADPH/minlmg protein in twins under epidural anesthesia as described previously in detail (8). 11.85 f 0.68 nM NADPHIminlmg protein in the ritodrine Catheters were placed in a fetal carotid artery, jugular vein, and infused twins, p < 0.001. There were no significant differ-the trachea. After the operation the fetuses received 200,000 U ences in hepatic total glycogen phosphorylase (a + b, of penicillin and 10 mg kanamycin intravenously every day, and activity, active (I) or total I + D) glycogen s~nthase activity, the ewes received 1.2 million U of procaine penicillin and 1 g of rotei in, or DNA content between the ritodrine treated and kanamycin intramuscularly daily for 5 days. The fetuses were control twins or between the control twins an...

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 93%

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Effects of β-2 Agonist on Hepatic Glycogen Metabolism in the Fetal Lamb

et al. 1988

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“…Glycogen phosphorylase (EC 2.4.1.1) activity was measured in the direction of glycogen breakdown, using a modification of previously described methods (27,38). The frozen lungs were homogenized on ice in 10 volumes (w/v) of a solution containing 100 mM NaF and 50 mM tris-succinate buffer, pH 6.9.…”

Section: Methodsmentioning

confidence: 99%

Delay in Pulmonary Glycogen Degradation in Fetuses of Streptozotocin Diabetic Rats

et al. 1982

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SummaryThe developmental profile of pulmonary glycogen was investigated in fetuses of rats made diabetic before conception with the injection of 40 mg/kg streptozotocin.Lungs of control litters showed increasing pulmonary glycogen concentration from day 16-20, followed by significant decline by term (= 22 days). In contrast, the diabetic litters, which had pulmonary glycogen concentration equal to controls until day 20, showed significantly higher glycogen values ( P < 0.01) on days 21and 22, consistent with a delay in glycogen degradation. This coincided with the fiding of decreased amounts of fetal pulmonary phosphatidylcholine and disaturated phosphatidylcholine on day 21 of the diabetic gestation (P < 0.05), but not before that time.Pulmonary glycogen phosphorylase A activity was significantly decreased in the diabetic litters on the final days of gestation, at the same time that the delay in glycogen breakdown became evident. Pulmonary glycogen synthase activity did not differ in the control and diabetic fetuses. SpeculationThe delay in pulmonary glycogen degradation seen in the fetus of the diabetic gestation is thus temporally related to the delay in lung maturation seen in this model and may be secondary to a decrease in the activity of the glycogenolytic enzyme phosphorylase A. Decreased availability of pulmonary glycogen stores for surfactant synthesis may be important in elucidating the mechanism of the delayed pulmonic maturation seen in fetuses of diabetic pregnancies.There is a growing body of evidence that implicates glucose, and its storage form glycogen, in the biosynthesis of surface active phospholipids in the developing fetus (11,36,42). Pulmonary glycogen content, which increases throughout most of gestation, falls rapidly near term, coincident with the appearance of lamellar bodies in alveolar type I1 cells and with an increase in choline incorporation into the surface active ~h o s~h o l i~i d fraction (27. 44). fhese maturational processes-the ialI & pu&onary glycogen; the rise in surfactant svnthesis, and the amearance of lamellar bodies-are all accelerated by the admini'siration of exogenous glucocorticoids (14,23,29,31,32). In a retrospective analysis, Robert et al. (3 1 ) showed that infants of diabetic pregnancies have a 5.6 times greater risk of developing the respiratory distress syndrome than those of nondiabetic gestations. It might therefore be expected that fetuses of diabetic pregnancies would have coincident aberrations in surfactant production and pulmonary glycogen metabolism. Indeed, increased pulmonary glycogen stores have been observed in fetal (39) and newborn (35) animals born to diabetic mothers; however, others report diminished glycogen content in the lungs of fetuses of experimental diabetic pregnancies (43).We used the streptozotocin diabetic rat as a means of studying fetal pulmonary glycogen metabolism throughout the diabetic gestation, in an effort to clarify the role of substrate availability with respect to the observed delay in lung maturation seen in the di...

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“…Tissues were maintained at -90°C for 1-2 years until use. Fetal liver samples from first trimester (8 weeks and 14 weeks) and midgestation aborted fetuses were obtained as previously described [14]. Tissues were maintained at -90°C for 12 years until use.…”

Section: Human Livermentioning

confidence: 99%

Cell‐free synthesis and co‐translational processing of the human asialoglycoprotein receptor

Breitfeld

Schwartz

1985

European Journal of Biochemistry

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The human asialoglycoprotein receptor is a 46-kDa membrane glycoprotein. It is initially synthesized as a 40-kDa precursor species possessing two N-linked high-mannose oligosaccharides which is subsequently converted to the 46-kDa mature product upon modification of its oligosaccharides of the complex form J. Biol. Chem. 258, 11 249-11 2551. To investigate further the biosynthesis of the human asialoglycoprotein receptor, we have utilized a cell-free wheat germ translation system supplemented with dog pancreatic microsomal membranes and programmed with HepG2 and human liver RNA. The primary translation product of the human receptor is a single 34-kDa species and this species is expressed throughout human fetal and adult development. The primary translation product possesses no cleavable signal peptide and is cotranslationally glycosylated to form the 40-kDa precursor species. In addition, the human asialoglycoprotein receptor is co-translationally inserted into microsomal membranes such that a 4-kDa cytoplasmic tail is susceptible to trypsin digestion.The hepatic asialoglycoprotein receptor (ASGP-R) mediates the selective uptake of plasma glycoproteins whose terminal sialic acid has been removed [I, 21. These asialoglycoproteins bind to the ASGP-R via their exposed galactose residues and are internalized through receptormediated endocytosis [l, 21. Many details of the intracellular pathways followed by both the ligand (asialoglycoproteins) and the ASGP-R [3 -51, as well as the kinetic parameters of receptor-mediated endocytosis of asialoglycoproteins, are well established [6, 71. In addition, the biosynthesis and intracellular processing of the human ASGP-R has been investigated in the human hepatoma cell line HepG2 [8 -101. The human ASGP-R is initially synthesized as a 40-kDa precursor with two N-linked high-mannose oligosaccharides. This precursor is then converted to the mature 46-kDa product upon Golgi modification of its oligosaccharides to the complex form. From the Golgi, the mature 46-kDa product is rapidly (within 5-10 niin) transported to the cell surface [8]. In addition, both the 40-kDa precursor and the 46-kDa product are phosphorylated on residues which presumably reside on the cytoplasmic domain of the ASGP-R [lo]. While little is known about the primary structure of the human ASGP-R, the primary structure of the major rat ASGP-R has been determined by direct sequence analysis [I 11. This polypeptide of 283 amino acids possesses a stretch of hydrophobic residues near the amino terminus and contains three putative oligosaccharideattachment sites toward the carboxy terminus.In order to define further the details of the co-translational processing of the human ASGP-R and to investigate directly its insertion into the lipid bilayer, we have investigated the in vitro synthesis of the human ASGP-R in a cell-free wheat germ translation system supplemented with dog pancreatic microsomal membranes. Thus, the co-translational N-linked glycosylation and co-translational insertion and orientation of in v...

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Hormonal Regulation of Glycogen Metabolism in Human Fetal Liver: I. Normal Development and Effects of Dibutyryl Cyclic AMP, Glucagon, and Insulin in Liver Explants

Cited by 16 publications

References 14 publications

Effects of β-2 Agonist on Hepatic Glycogen Metabolism in the Fetal Lamb

Effects of β-2 Agonist on Hepatic Glycogen Metabolism in the Fetal Lamb

Delay in Pulmonary Glycogen Degradation in Fetuses of Streptozotocin Diabetic Rats

Cell‐free synthesis and co‐translational processing of the human asialoglycoprotein receptor

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