Turnover of liver glycogen in the rat foetus.
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ABSTRACT:
SUBMITTER: Gilbert M
PROVIDER: S-EPMC1186301 | biostudies-other | 1978 Dec
REPOSITORIES: biostudies-other
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Project description:Changes in the growth and protein turnover (measured in vivo) of the rat liver, kidney and whole body were studied between 16 days of life in utero and 105 weeks post partum. Tissue and whole-body growth were related to changes in both cellular hyperplasia (i.e. changes in DNA) and hypertrophy (protein/DNA values) and to the protein composition within the enlarging tissue mass. The suitability of using a single large dose of phenylalanine for measuring the rates of protein synthesis during both pre- and post-natal life was established. The declining growth rates in the whole animal and the two visceral tissues were then explained by developmental changes in the fractional rates of protein synthesis and breakdown, turnover rates being age-for-age higher in the liver than in the kidney, which in turn were higher than those measured in the whole animal. The declining fractional rates of synthesis in both tissues and the whole body with increasing age were related to changes in the tissues' ribosomal capacity and activity. The fall in the hepatic rate between 18 and 20 days of foetal life (from 134 to 98% per day) corresponded to a decrease in both the ribosomal capacity and the rate of synthesis per ribosome. No significant changes in any of these parameters were, however, found in the liver between weaning (3 weeks) and senility (105 weeks). In contrast, the fractional synthetic (and degradative) rates progressively declined in the kidney (from 95 to 24% per day) and whole body (from 70 to 11% per day) throughout both pre- and post-natal life, mainly as a consequence of a progressive decline in the ribosomal capacity, but with some fall in the ribosomal activity also during foetal life. The age-related contributions of these visceral tissues to the total amount of protein synthesized per day by the whole animal were determined. The renal contribution remained fairly constant at 1.6-2.9%, whereas the hepatic contribution declined from 56 to 11%, with increasing age. Approximate-steady-state conditions were reached at, and between, 44 and 105 weeks post partum, the half-life values of mixed whole-body, kidney and liver proteins being 6.4, 3.0 and 1.5 days, respectively, at 105 weeks.
| S-EPMC1153243 | biostudies-other
Project description:Two electrophoretically distinguishable metallothioneins were isolated from the livers of Cd2+-treated rats and had thiol group/metal ratios of 3:1, a total metal content, in each of these proteins, of 3.6 atoms of Cd2+ + 2.4 atoms of Zn2+/molecule and 4.2 atoms of Cd2+ + 2.8 atoms of Zn2+/molecule and respective apoprotein mol.wts. of 5844 and 6251. Studies with 1 h pulse labels of [3H]cysteine, given after a single injection of ZnCl2 or CdCl2, showed that these metals stimulated radioactive isotope incorporation into the metallothioneins over the control value by 10- and 15-fold respectively. This stimulation was maximal at 4 h after a single CdCl2 injection and decreased to control values by 16 h, suggesting that either a translational event is responding to free intracellular Cd2+ or a short-lived mRNA is being produced or stabilized in response to the metal treatment. In rats chronically exposed to CdCl2, the metallothioneins increased to 0.2% of the liver wet weight from a control value of 2--4 mumol/kg of liver, with a maximum rate of accumulation of 2--3 mumol/h per kg of liver. The turnover of these proteins in control animals was 0.3--0.6 mumoles/h per kg of liver, measured by the rate of disappearance of 203Hg2+, which binds irreversibly to the metallothioneins. Pretreatment with CdCl2 completely stopped the rapid 203Hg turnover observed in untreated animals. Unlike CdCl2, treatment with ZnCl2 increased the concentration of metallothioneins to a new steady-state pool, 11 mumole/kg of liver, after 10 h. The increase in the zinc-thionein pool by exposure to ZnCl2 in vivo was determined to be primarily due to a stimulation of metallothionein biosynthesis.
| S-EPMC1185914 | biostudies-other
Project description:Glycogen is a highly branched glucose polymer which is involved in maintaining blood-sugar homeostasis. Liver glycogen contains large composite ? particles made up of linked ? particles. Previous studies have shown that the binding which links ? particles into ? particles is impaired in diabetic mice. The present study reports the first molecular structural characterization of human-liver glycogen from non-diabetic patients, using transmission electron microscopy for morphology and size-exclusion chromatography for the molecular size distribution; the latter is also studied as a function of time during acid hydrolysis in vitro, which is sensitive to certain structural features, particularly glycosidic vs. proteinaceous linkages. The results are compared with those seen in mice and pigs. The molecular structural change during acid hydrolysis is similar in each case, and indicates that the linkage of ? into ? particles is not glycosidic. This result, and the similar morphology in each case, together imply that human liver glycogen has similar molecular structure to those of mice and pigs. This knowledge will be useful for future diabetes drug targets.
| S-EPMC4775040 | biostudies-literature
Project description:1. The total activity of glycogen synthease increased 20-fold from day 17 of gestation to birth at day 22, with a further increase of 18% in the 24h after birth. Active synthase (I) rose 45-fold to a maximum at day 21, fell 40% before birth, and then increased by a similar amount 24h after birth. The fraction of synthase in the active form correlated very well with the deposition of glycogen in the liver. 2. Total phosphorylase had a similar developmental pattern of total synthease with an 18-fold increase from day 17 to day 22. The appearance of active phosphorylase showed a lag-period compared with total phosphorylase and did not increase significantly until day 20. The fraction of phosphorylase in the active form did not correlate at all with glycogen deposition or mobilization. 3. There was a close relationshp between the ratio of phosphorylase a/synthase I and the glycogen content of the liver. An increase or decrease in this ratio would result in glycogenolysis of glycogenesis respectively. 4. It is postulated that a cycle between the two enzymes under basal conditions could exist which permits a continuous turnover of glycogen. Such a system would explain why active phosphorylase is always seen, even under conditions of net glycogen synthesis. The differences in hormone sensitivity of synthase and phosphorylase would also be accounted for as only one enzyme would have to respond acutely to hormonal influences.
| S-EPMC1164232 | biostudies-other
Project description: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.
| S-EPMC1168004 | biostudies-other
Project description:1. The development of active and inactive phosphorylase was determined in rat liver during the perinatal period. No inactive form could be found in tissues from animals less than 19 days gestation or older than the fifth postnatal day. 2. The regulation of phosphorylase in organ cultures of foetal rat liver was examined. None of the agents examined [glucagon, insulin or dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate)] changed the amount of phosphorylase activity. 3. Glycogen concentration in these explants were nevertheless decreased more than twofold by 4h of incubation with glucagon or dibutyryl cyclic AMP. Incubation with insulin for 4h increased the glycogen content twofold. 4. Glycogen synthetase activity was examined in these explants. I-form activity (without glucose 6-phosphate) was found to decrease by a factor of two after 4h of incubation with dibutyryl cyclic AMP, whereas I+D activity (with glucose 6-phosphate) remained nearly constant. Incubation for 4h with insulin increased I-form activity threefold, with only a slight increase in I+D activity. 5. When explants were incubated with insulin followed by addition of dibutyryl cyclic AMP, the effects of insulin on glycogen concentration and glycogen synthetase activity were reversed. 6. These results indicate that the regulation of glycogen synthesis may be the major factor in the hormonal control of glycogen metabolism in neonatal rat liver.
| S-EPMC1177906 | biostudies-other
Project description:Identification and relative quantification of proteins associated with mammalian liver glycogen.
2018-07-23 | PXD009140 | Pride
Project description:1. In the isolated perfused liver from 48h-starved rats, glycogen synthesis was followed by sequential sampling of the two major lobes. 2. The fastest observed rates of glycogen deposition (0.68-0.82mumol of glucose/min per g fresh liver) were obtained in the left lateral lobe, when glucose in the medium was 25-30mm and when gluconeogenic substrates were present (pyruvate, glycerol and serine: each initially 5mm). In this situation there was no net disappearance of glucose from the perfusion medium, although (14)C from [U-(14)C]glucose was incorporated into glycogen. There was no requirement for added hormones. 3. In the absence of gluconeogenic precursors, glycogen synthesis from glucose (30mm) was 0-0.4mumol/min per g. 4. When livers were perfused with gluconeogenic precursors alone, no glycogen was deposited. The total amount of glucose formed was similar to the amount converted into glycogen when 30mm-glucose was also present. 5. The time-course, maximal rates and glucose dependence of hepatic glycogen deposition in the perfused liver resembled those found in vivo in 48h-starved rats, during infusion of glucose. 6. In the perfused liver, added insulin or sodium oleate did not significantly affect glycogen synthesis in optimum conditions. In suboptimum conditions (i.e. glucose less than 25mm, or with gluconeogenic precursors absent) insulin caused a moderate acceleration of glycogen deposition. 7. These results suggest that on re-feeding after starvation in the rat, hepatic glycogen deposition could be initially the result of continued gluconeogenesis, even after the ingestion of glucose. This conclusion is discussed, particularly in connexion with the role of hepatic glucokinase, and the involvement of the liver in the glucose intolerance of starvation.
| S-EPMC1174156 | biostudies-other
Project description:Glycogen is the largest soluble cytosolic macromolecule and considered as the principal storage form of glucose. Cancer cells generally increase their glucose consumption and rewire their metabolism towards aerobic glycolysis to promote growth. Here we report that glycogen accumulation is a key initiating oncogenic event and essential for malignant transformation. RNA-sequencing analysis reveals that G6PC, an enzyme catalyzing the last step of glycogenolysis, is frequently downregulated to augment glucose storage in pro-tumor cells. Accumulated glycogen undergoes liquid-liquid phase separation undergoes liquid-liquid phase separation, which results in the assembly of the laforin-Mst1/2 complex and consequently traps Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme PYGL deficiency in both human and mice result in glycogen storage disease with enlarged liver size and cancer development, phenocopying Hippo deficiency. Consistently, elimination of glycogen accumulation abrogates liver enlargement and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that glycogen not only provides nutrition and energy to the cells but also functions as a key initiating oncogenic metabolite, which physically blocks Hippo signaling through glycogen phase separation to augment pro-tumor cell initiation and progression.
2021-10-06 | GSE148933 | GEO
Project description:Glycogen storage disease type I (GSDI), an inborn error of carbohydrate metabolism, is caused by defects in the glucose-6-transporter/glucose-6-phosphatase complex, which is essential in glucose homeostasis. Two types exist, GSDIa and GSDIb, each caused by different defects in the complex. GSDIa is characterized by fasting intolerance and subsequent metabolic derangements. In addition to these clinical manifestations, patients with GSDIb suffer from neutropenia with neutrophil dysfunction and inflammatory bowel disease.With the feasibility of novel cell-based therapies, including hepatocyte transplantations and liver stem cell transplantations, it is essential to consider long term outcomes of liver replacement therapy. We reviewed all GSDI patients with liver transplantation identified in literature and through personal communication with treating physicians. Our review shows that all 80 GSDI patients showed improved metabolic control and normal fasting tolerance after liver transplantation. Although some complications might be caused by disease progression, most complications seemed related to the liver transplantation procedure and subsequent immune suppression. These results highlight the potential of other therapeutic strategies, like cell-based therapies for liver replacement, which are expected to normalize liver function with a lower risk of complications of the procedure and immune suppression.
| S-EPMC4113191 | biostudies-literature