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Glycogen metabolism in the liver of the foetal rat.

ABSTRACT: 1. The glycogen present in the liver of rat foetuses was labelled by injecting a trace amount of [6-(3)H]glucose into the mother at 19.5 days of gestation. The radioactivity incorporated in the glycogen 4h after the administration of the label was still present 38h later. A large proportion of this radioactivity was on the outer chains of the polysaccharide. These results indicate that there is normally almost no glycogen degradation in the foetal liver. In contrast, glycogen breakdown occurs very rapidly in the livers of foetuses whose mother is anaesthetized. 2. Glycogen synthetase is present in the liver at day 16 of gestation at a concentration as high as 30% of that in the adult, but essentially as an inactive (b) enzyme. The appearance of synthetase phosphatase between days 18 and 19 corresponds to that of synthetase a and to the beginning of glycogen synthesis. From day 19 to 21.5 the amount of synthetase a present in the foetal liver is just sufficient to account for the actual rate of glycogen deposition. 3. The content of total phosphorylase in the foetal liver increases continuously from day 16 to birth. However, a precise measurement of the a and b forms of the enzyme in the liver of non-anaesthetized foetuses is not possible. Taking the rate of glycogenolysis as an appropriate index of phosphorylase activity, we conclude that this enzyme is almost entirely in the inactive form in the foetal liver under normal conditions. 4. The accumulation of glycogen in the liver during late pregnancy may therefore be explained by a relatively slow rate of synthesis and a nearly total absence of degradation.

SUBMITTER: Devos P

PROVIDER: S-EPMC1168004 | biostudies-other | 1974 May

REPOSITORIES: biostudies-other

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

Project description: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'.

| S-EPMC1162376 | biostudies-other

Glycogen metabolism in the liver of the developing rat.

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| S-EPMC1164232 | biostudies-other

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| S-EPMC3953428 | biostudies-literature

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2013-09-02 | E-GEOD-30139 | biostudies-arrayexpress

Glycogen metabolism and glycogen storage disorders.

Project description:Glucose is the main energy fuel for the human brain. Maintenance of glucose homeostasis is therefore, crucial to meet cellular energy demands in both - normal physiological states and during stress or increased demands. Glucose is stored as glycogen primarily in the liver and skeletal muscle with a small amount stored in the brain. Liver glycogen primarily maintains blood glucose levels, while skeletal muscle glycogen is utilized during high-intensity exertion, and brain glycogen is an emergency cerebral energy source. Glycogen and glucose transform into one another through glycogen synthesis and degradation pathways. Thus, enzymatic defects along these pathways are associated with altered glucose metabolism and breakdown leading to hypoglycemia ± hepatomegaly and or liver disease in hepatic forms of glycogen storage disorder (GSD) and skeletal ± cardiac myopathy, depending on the site of the enzyme defects. Overall, defects in glycogen metabolism mainly present as GSDs and are a heterogenous group of inborn errors of carbohydrate metabolism. In this article we review the genetics, epidemiology, clinical and metabolic findings of various types of GSD, and glycolysis defects emphasizing current treatment and implications for future directions.

| S-EPMC6331362 | biostudies-literature

Role of Per2 in the control of liver glycogen metabolism

2013-09-02 | GSE30139 | GEO

Chronic liver disease and impaired hepatic glycogen metabolism in argininosuccinate lyase deficiency.

Project description:BACKGROUNDLiver disease in urea cycle disorders (UCDs) ranges from hepatomegaly and chronic hepatocellular injury to cirrhosis and end-stage liver disease. However, the prevalence and underlying mechanisms are unclear.METHODSWe estimated the prevalence of chronic hepatocellular injury in UCDs using data from a multicenter, longitudinal, natural history study. We also used ultrasound with shear wave elastography and FibroTest to evaluate liver stiffness and markers of fibrosis in individuals with argininosuccinate lyase deficiency (ASLD), a disorder with high prevalence of elevated serum alanine aminotransferase (ALT). To understand the human observations, we evaluated the hepatic phenotype of the AslNeo/Neo mouse model of ASLD.RESULTSWe demonstrate a high prevalence of elevated ALT in ASLD (37%). Hyperammonemia and use of nitrogen-scavenging agents, 2 markers of disease severity, were significantly (P < 0.001 and P = 0.001, respectively) associated with elevated ALT in ASLD. In addition, ultrasound with shear wave elastography and FibroTest revealed increased echogenicity and liver stiffness, even in individuals with ASLD and normal aminotransferases. The AslNeo/Neo mice mimic the human disorder with hepatomegaly, elevated aminotransferases, and excessive hepatic glycogen noted before death (3-5 weeks of age). This excessive hepatic glycogen is associated with impaired hepatic glycogenolysis and decreased glycogen phosphorylase and is rescued with helper-dependent adenovirus expressing Asl using a liver-specific (ApoE) promoter.CONCLUSIONOur results link urea cycle dysfunction and impaired hepatic glucose metabolism and identify a mouse model of liver disease in the setting of urea cycle dysfunction.TRIAL REGISTRATIONThis study has been registered at ClinicalTrials.gov (NCT03721367, NCT00237315).FUNDINGFunding was provided by NIH, Burroughs Wellcome Fund, NUCDF, Genzyme/ACMG Foundation, and CPRIT.

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| S-EPMC1215193 | biostudies-other

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