Hormonal regulation of glycogen metabolism in neonatal rat liver.
Ontology highlight
ABSTRACT:
SUBMITTER: Schwartz AL
PROVIDER: S-EPMC1177906 | biostudies-other | 1973 Aug
REPOSITORIES: biostudies-other
Similar Datasets
Project description:1. The metabolism of hepatic glycogen, labelled with [6-3H]glucose at day 19.5 of gestation and with 14C from [U-14C]galactose at delivery, was followed for 10 h in food-deprived gsd/gsd and control (GSD/GSD) neonatal rats. 2. In the affected pups glycogen was maintained at 12% (w/w) and there was no loss of incorporated radioactivity. 3. The 3H and 14C in glycogen from the controls were both decreased by 80%, but 14C was removed at 0--5 h and [6-3H]glucose at 5--10 h. 4. Blood glucose concentrations in the unaffected neonatal rats fell from 5.3 mM at 20 min to 1.7 mM after 10 h. In the gsd/gsd pups blood glucose concentration was decreased from 2 mM at birth to 0.3 mM at 2.5 h: it was maintained at 0.8 mM between 5 and 10 h. 5. In neonatal rats that had been dead for 10 h, hepatic glycogen was decreased by 34% in the controls and by 22% in the gsd/gsd pups. These results demonstrate that liver from the affected rats contains glycogenolytic activity, but that it is not expressed in living tissue.
| S-EPMC1158155 | biostudies-other
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:It has been reported that Cavin1 deficiency causes lipodystrophy in both humans and mice by affecting lipid metabolism. The ablation of Cavin1 in rodents also causes a significant deviation from Mendelian ratio at weaning in a background-dependent manner, suggesting the presence of undiscovered functions of Cavin1. In the current study, the results show that Cavin1 deficiency causes neonatal death in C57BL/6J mice by dampening the storage and mobilization of glycogen in the liver, which leads to lethal neonatal hypoglycemia. Further investigation by electron microscopy reveals that Cavin1 deficiency impairs the fenestration in liver sinusoidal endothelial cells (LSECs) and impacts the permeability of endothelial barrier in the liver. Mechanistically, Cavin1 deficiency inhibits the RhoA-Rho-associated protein kinase 2-LIM domain kinase-Cofilin signaling pathway and suppresses the dynamics of the cytoskeleton, and eventually causes the reduction of fenestrae in LSECs. In addition, the defect of fenestration in LSECs caused by Cavin1 deficiency can be rescued by treatment with the F-actin depolymerization reagent latrunculin A. In summary, the current study reveals a novel function of Cavin1 on fenestrae formation in LSECs and liver glycogen metabolism, which provide an explanation for the neonatal death of Cavin1 null mice and a potential mechanism for metabolic disorders in patients with Cavin1 mutation.
| S-EPMC7539207 | biostudies-literature
Project description:Microorganisms have the capacity to utilize a variety of nutrients and adapt to continuously changing environmental conditions. Many microorganisms, including yeast and bacteria, accumulate carbon and energy reserves to cope with the starvation conditions temporarily present in the environment. Glycogen biosynthesis is a main strategy for such metabolic storage, and a variety of sensing and signaling mechanisms have evolved in evolutionarily distant species to ensure the production of this homopolysaccharide. At the most fundamental level, the processes of glycogen synthesis and degradation in yeast and bacteria share certain broad similarities. However, the regulation of these processes is sometimes quite distinct, indicating that they have evolved separately to respond optimally to the habitat conditions of each species. This review aims to highlight the mechanisms, both at the transcriptional and at the post-transcriptional level, that regulate glycogen metabolism in yeast and bacteria, focusing on selected areas where the greatest increase in knowledge has occurred during the last few years. In the yeast system, we focus particularly on the various signaling pathways that control the activity of the enzymes of glycogen storage. We also discuss our recent understanding of the important role played by the vacuole in glycogen metabolism. In the case of bacterial glycogen, special emphasis is placed on aspects related to the genetic regulation of glycogen metabolism and its connection with other biological processes.
| S-EPMC2927715 | biostudies-literature
Project description:Nrf2 (NF-E2-related factor 2) contributes to the maintenance of glucose homeostasis in vivo Nrf2 suppresses blood glucose levels by protecting pancreatic β cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1 knockout (Keap1MuKO) mice that express abundant Nrf2 in their SkM and then examined Nrf2 target gene expression in that tissue. In Keap1MuKO mice, blood glucose levels were significantly downregulated and the levels of the glycogen branching enzyme (Gbe1) and muscle-type PhKα subunit (Phka1) mRNAs, along with those of the glycogen branching enzyme (GBE) and the phosphorylase b kinase α subunit (PhKα) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2 inducers promoted Gbe1 and Phka1 mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 and Phka1 upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was strongly reduced and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2 induction in SkM increases GBE and PhKα expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Our results also indicate that Nrf2 differentially regulates glycogen metabolism in SkM and the liver.
| S-EPMC4959318 | biostudies-literature
Project description:BackgroundVentromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression.MethodsThe aromatase inhibitor letrozole (LZ) was used with high-resolution microdissection/Western blot techniques to address the hypothesis that neuroestradiol exerts sex-dimorphic control of VMN neuronal nitric oxide synthase (nNOS) and glutamate decarboxylase65/67 (GAD) protein expression. Glycogen metabolism impacts VMN nNOS and GAD profiles; here, LZ treatment effects on VMN glycogen synthase (GS) and phosphorylase brain- (GPbb; glucoprivic-sensitive) and muscle (GPmm; norepinephrine-sensitive) variant proteins were examined.ResultsVMN aromatase protein content was similar between sexes. Intracerebroventricular LZ infusion of testes-intact male and ovariectomized, estradiol-replaced female rats blocked insulin-induced hypoglycemic (IIH) up-regulation of this profile. LZ exerted sex-contingent effects on basal VMN nNOS and GAD expression, but blocked IIH-induced NO stimulation and GAD suppression in each sex. Sex-contingent LZ effects on basal and hypoglycemic patterns of GPbb and GPmm expression occurred at distinctive levels of the VMN. LZ correspondingly down- or up-regulated baseline pyruvate recycling pathway marker protein expression in males (glutaminase) and females (malic enzyme-1), and altered INS effects on those proteins.ConclusionsResults infer that neuroestradiol is required in each sex for optimal VMN metabolic transmitter signaling of hypoglycemic energy deficiency. Sex differences in VMN GP variant protein levels and sensitivity to aromatase may correlate with sex-dimorphic glycogen mobilization during this metabolic stress. Neuroestradiol may also exert sex-specific effects on glucogenic amino acid energy yield by actions on distinctive enzyme targets in each sex.
| S-EPMC7687823 | biostudies-literature
Project description:BackgroundDuchenne muscular dystrophy (DMD) is a severe, genetic muscle wasting disorder characterised by progressive muscle weakness. DMD is caused by mutations in the dystrophin (dmd) gene resulting in very low levels or a complete absence of the dystrophin protein, a key structural element of muscle fibres which is responsible for the proper transmission of force. In the absence of dystrophin, muscle fibres become damaged easily during contraction resulting in their degeneration. DMD patients and mdx mice (an animal model of DMD) exhibit altered metabolic disturbances that cannot be attributed to the loss of dystrophin directly. We tested the hypothesis that glycogen metabolism is defective in mdx dystrophic mice.ResultsDystrophic mdx mice had increased skeletal muscle glycogen (79%, (P<0.01)). Skeletal muscle glycogen synthesis is initiated by glycogenin, the expression of which was increased by 50% in mdx mice (P<0.0001). Glycogen synthase activity was 12% higher (P<0.05) but glycogen branching enzyme activity was 70% lower (P<0.01) in mdx compared with wild-type mice. The rate-limiting enzyme for glycogen breakdown, glycogen phosphorylase, had 62% lower activity (P<0.01) in mdx mice resulting from a 24% reduction in PKA activity (P<0.01). In mdx mice glycogen debranching enzyme expression was 50% higher (P<0.001) together with starch-binding domain protein 1 (219% higher; P<0.01). In addition, mdx mice were glucose intolerant (P<0.01) and had 30% less liver glycogen (P<0.05) compared with control mice. Subsequent analysis of the enzymes dysregulated in skeletal muscle glycogen metabolism in mdx mice identified reduced glycogenin protein expression (46% less; P<0.05) as a possible cause of this phenotype.ConclusionWe identified that mdx mice were glucose intolerant, and had increased skeletal muscle glycogen but reduced amounts of liver glycogen.
| S-EPMC3953428 | biostudies-literature
Project description:BackgroundCD36 is a multiligand receptor involved in various metabolic pathways, including cellular uptake of long-chain fatty acids. Defect function or expression of CD36 can result in dyslipidemia or insulin resistance. We have previously shown that CD36 expression is female-predominant in rat liver. In the present study, hormonal and nutritional regulation of hepatic CD36 expression was examined in male and female rats. Since alternative transcription start sites have been described in murine and human Cd36, we investigated whether alternative CD36 transcripts are differentially regulated in rat liver during these conditions.ResultsSequence information of the rat Cd36 5'-UTR was extended, showing that the gene structure of Cd36 in rat is similar to that previously described in mouse with at least two alternative first exons. The rat Cd36 exon 1a promoter was sequenced and found to be highly similar to murine and human Cd36. We show that alternative first exon usage is involved in the female-predominant expression of CD36 in rat liver and during certain hormonal states that induce CD36 mRNA abundance. Estrogen treatment or continuous infusion of growth hormone (GH) in male rats induced CD36 expression preferentially through the exon 1a promoter. Old age was associated with increased CD36 expression in male rats, albeit without any preferential first exon usage. Intermittent GH treatment in old male rats reversed this effect. Mild starvation (12 hours without food) reduced CD36 expression in female liver, whereas its expression was increased in skeletal muscle.ConclusionThe results obtained in this study confirm and extend our previous observation that GH is an important regulator of hepatic CD36, and depending on the mode of treatment (continuous or intermittent) the gene might be either induced or repressed. We suggest that the effects of continuous GH secretion in females (which is stimulatory) and intermittent GH secretion in males (which is inhibitory) explains the sex-different expression of this gene. Furthermore, a female-specific repression of hepatic CD36 in response to food deprivation was found, which was in contrast to a stimulatory effect in skeletal muscle. This demonstrates a tissue-specific regulation of Cd36.
| S-EPMC1934915 | biostudies-literature
Project description:To investigate the role of Per2 in glucose metabolism in-vivo we used mice bearing a targeted gene mutation in the Per2 gene (Per2brdm) and thus unable to express a functional Per2 protein. Mice were hosted in our standard mouse facility in a 12-hour light and 12-hour dark cycle. Wt and Per2brdm mice were fed with either standard chow diet or high-fat diet for 24 weeks and analyzed for glucose homeostasis. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed on mice food deprived for 7 hours. For pyruvate tolerance test (PTT) mice were fasted for 14 hours. Glucose levels were measured over 12 hours starvation time-courses during the light and the dark phase. Fed and fasting blood glucose and hepatic glycogen content were measured over different circadian time-points. To investigate the role of Per2 in the control of liver gene expression we performed DNA-microarray analysis of RNA preparations from liver of Per2brdm and WT mice. We extracted total RNA from liver of four different Per2brdm and WT mice. Mice from the same cohort were sacrificed after 8 hours of starvation. After normalization we performed a fold change comparison selecting probes with a p value < 0.05.
2013-09-02 | E-GEOD-30139 | biostudies-arrayexpress