scholarly journals Hepatic carbon flux after re-feeding. Hyperthyroidism blocks glycogen synthesis and the suppression of glucose output observed in response to carbohydrate re-feeding

1987 ◽  
Vol 247 (3) ◽  
pp. 627-634 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Intragastric Administration ◽  
Indirect Pathway ◽  
Glucose Flux ◽  
Glucose Output ◽  
Dehydrogenase Complex

1. The work investigated hepatic glycogen synthesis and glucose output after the intragastric administration of glucose or glycerol or the provision of chow ad libitum to 48 h-starved euthyroid or hyperthyroid rats. 2. After glucose administration, glycogen synthesis via the indirect pathway [Newgard, Hirsch, Foster & McGarry (1983) J. Biol. Chem. 258, 8046-8052] occurred concomitantly with reversal of glucose flux across the liver and re-activation of pyruvate kinase in the euthyroid controls. Glycogen synthesis was decreased and net glucose output continued in the hyperthyroid rats, but normal re-activation of pyruvate kinase was observed. 3. Use of 3-mercaptopicolinate indicated that the glucose released from liver of hyperthyroid rats was synthesized from substrates metabolized via the gluconeogenic pathway. 4. Hepatic glycogen synthesis was also impaired in hyperthyroid rats after administration of glycerol or chow. Measurement of portal-minus-hepatovenous concentration differences and arterial glucose concentrations after the administration of glycerol in combination with 3-mercaptopicolinate indicated that flux from triose phosphate to glucose 6-phosphate was not decreased. 5. Inhibited glycogen synthesis after chow re-feeding was associated with accelerated re-activation of hepatic pyruvate dehydrogenase complex in the hyperthyroid rats. 6. The results indicate three distinct and independent actions of hyperthyroidism after re-feeding: (i) it inhibits the reversal of glucose flux across the liver normally observed in response to carbohydrate; (ii) it affects glycogen deposition at a site distal to glucose 6-phosphate; (iii) it allows more rapid re-activation of liver pyruvate dehydrogenase complex in response to a mixed diet.

scholarly journals Hepatic glycogen synthesis on carbohydrate re-feeding after starvation. A regulatory role for pyruvate dehydrogenase in liver and extrahepatic tissues

1986 ◽  
Vol 235 (2) ◽  
pp. 441-445 ◽  
Author(s):  
M J Holness ◽  
T J French ◽  
M C Sugden
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Synthesis ◽  
Regulatory Role ◽  
Hepatic Glycogen ◽  
Glucose Administration ◽  
Hepatic Glucose ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Dehydrogenase Complex

Glucose administration to 48 h-starved rats increased hepatic glucose, lactate, pyruvate and glycogen concentrations and re-activated PDH (pyruvate dehydrogenase complex) in kidney, but not in heart or liver. Dichloroacetate together with glucose re-activated PDH in all three tissues, decreased hepatic lactate and pyruvate concentrations and impaired glycogen resynthesis. Thus on re-feeding, delayed PDH re-activation is important for provision of precursors for hepatic glyconeogenesis.

Hepatic glycogen accurately reflected by acetaminophen glucuronide in dogs refed after fasting

1995 ◽  
Vol 269 (4) ◽  
pp. E766-E773 ◽  
Author(s):  
K. I. Rother ◽  
W. F. Schwenk
Keyword(s):  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Isotopic Tracers ◽  
Glucose Flux ◽  
Liver Biopsies ◽  
The Mean ◽  
Acetaminophen Glucuronide ◽  
Group 2

To validate a method to “biochemically biopsy” the immediate precursor of intrahepatic glycogen [uridyl diphosphate (UDP)-glucose] using acetaminophen and to assess how fasting affects the direct and indirect pathways of glycogen synthesis, dogs were fasted overnight (group 1, n = 5) or for 2.5 days (group 2, n = 5) and then given a 4-h duodenal infusion of unlabeled glucose, [3-3H]glucose, and [U-14C]lactate to label hepatic glycogen via the direct and indirect pathways, respectively, and [1-13C]galactose to measure intrahepatic UDP-glucose flux. After 3 h for equilibration, acetaminophen was given and urine was collected for acetaminophen glucuronide. Multiple liver biopsies were obtained. The mean 3H/14C ratios of glucose derived from glycogen (10.4 +/- 4.1 and 1.1 +/- 0.3 for groups 1 and 2, respectively) and glucose derived from acetaminophen glucuronide (11.5 +/- 4.0 and 1.0 +/- 0.1 for groups 1 and 2, respectively) were similar. Fasting significantly increased UDP-glucose flux, the rate of glycogen synthesis, and the contribution of the indirect pathway. We conclude that, in dogs, 1) no functional hepatic zonation exists with regard to acetaminophen glucuronidation and liver glycogen synthesis and 2) with appropriate choice of isotopic tracers and study design, UDP-glucose flux can accurately reflect rates of hepatic glycogen synthesis.

Ontogeny of pyruvate dehydrogenase complex and key enzymes involved in glycolysis and tricarboxylic acid cycle in rabbit fetal lung, heart, and liver

1990 ◽  
Vol 68 (10) ◽  
pp. 1210-1217 ◽  
Author(s):  
Bhagu R. Bhavnani ◽  
Duncan G. Wallace
Keyword(s):  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fetal Liver ◽  
Tricarboxylic Acid Cycle ◽  
Pyruvate Dehydrogenase Complex ◽  
Fetal Lung ◽  
Tricarboxylic Acid ◽  
Acid Cycle ◽  
Key Enzymes ◽  
Dehydrogenase Complex

The metabolic pathways by which the glycogen is utilized by fetal tissues is not well established. In the present study the ontogeny of seven key enzymes involved in glycolysis and the tricarboxylic acid cycle has been established for rabbit fetal lung, heart, and liver. In the fetal lung the activities of phosphofructokinase, pyruvate kinase, lactic dehydrogenase, citrate synthase, and malate dehydrogenase increase from day 21 to 25. Thereafter the levels either drop to day 19 levels or do not change. The isocitrate dehydrogenase activity continues to increase from day 19 of gestation to maximum level on day 31 of gestation. In fetal heart the pattern of activity is similar, but in fetal liver most of the enzymes reach maximum levels earlier and, with the exception of pyruvate kinase, do not show a significant fall in activity near term. The pattern of development of pyruvate dehydrogenase complex is different; maximum activity is observed on day 27 in fetal lung and heart and on day 21 in fetal liver. These results indicate that all three fetal tissues can oxidize glucose. Also, the accumulation of glycogen, particularly in fetal lung, appears to ensure that at specific times during gestation adequate quantities of energy (ATP) and substrates, required for surfactant phospholipid synthesis, are available independent of maternal supply of glucose or during brief episodes of hypoxia.Key words: glycogen, glycolysis, tricarboxylic acid cycle, pyruvate dehydrogenase, surfactant.

scholarly journals Hepatic carbon flux after re-feeding in the glycogen-storage-disease (gsd/gsd) rat

1987 ◽  
Vol 248 (3) ◽  
pp. 969-972 ◽  
Author(s):  
M J Holness ◽  
T N Palmer ◽  
E B Worrall ◽  
M C Sugden
Keyword(s):  
Glycogen Storage Disease ◽  
Pyruvate Dehydrogenase ◽  
Carbon Flux ◽  
Storage Disease ◽  
Pyruvate Dehydrogenase Complex ◽  
Glycogen Storage ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Glucose Output ◽  
Dehydrogenase Complex

In this study we utilized the phosphorylase b kinase-deficient (gsd/gsd) rat as a model of hepatic substrate utilization where there is a constraint on glycogenesis imposed by the maintenance of high glycogen concentrations. Glucose re-feeding of 48 h-starved gsd/gsd rats led to suppression of hepatic glucose output. In contrast with the situation in normal rats, activation of the pyruvate dehydrogenase complex and lipogenesis was observed. It is suggested that impeding glycogenic flux may divert substrate into lipogenesis, possibly via activation of the pyruvate dehydrogenase complex.

Metabolic Effects of Metformin in Humans

2019 ◽  
Vol 15 (4) ◽  
pp. 328-339 ◽  
Author(s):  
María M. Adeva-Andany ◽  
Eva Rañal-Muíño ◽  
Carlos Fernández-Fernández ◽  
Cristina Pazos-García ◽  
Matilde Vila-Altesor
Keyword(s):  
Insulin Resistance ◽  
Glycogen Synthesis ◽  
Metabolic Effects ◽  
Hepatic Glycogen ◽  
Insulin Deficiency ◽  
Indirect Pathway ◽  
Hepatic Glucose Output ◽  
Hepatic Glucose ◽  
Patients With Diabetes ◽  
Glucose Output

Background: Both insulin deficiency and insulin resistance due to glucagon secretion cause fasting and postprandial hyperglycemia in patients with diabetes. Introduction: Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive. Results: Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen synthesis from “de novo” synthesized glucose) owing to insulin deficiency and glucagoninduced insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production. In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity. Accordingly, metformin preserves β-cell function in patients with type 2 diabetes. Conclusion: Several mechanisms have been proposed to explain the metabolic effects of metformin, but evidence is not conclusive and the molecular basis of metformin action remains unknown.

scholarly journals Pyruvate dehydrogenase activities during the fed-to-starved transition and on re-feeding after acute or prolonged starvation

1989 ◽  
Vol 258 (2) ◽  
pp. 529-533 ◽  
Author(s):  
M J Holness ◽  
M C Sugden
Keyword(s):  
Acute Phase ◽  
Pyruvate Dehydrogenase ◽  
Temporal Relationship ◽  
Pyruvate Dehydrogenase Complex ◽  
Hepatic Glycogen ◽  
Dietary Carbohydrate ◽  
Glycogen Depletion ◽  
Prolonged Starvation ◽  
Complex Activities ◽  
Dehydrogenase Complex

We investigated the temporal relationship between hepatic glycogen depletion and cardiac and hepatic PDH (pyruvate dehydrogenase complex) activities during the acute phase of starvation. There was a striking correlation between the decline in hepatic glycogen and PDH inactivation during the first 10 h of starvation. Re-feeding after 6 h starvation was associated with complete re-activation of PDH in liver and re-activation to approx. 75% of the fed value in heart, whereas in rats previously starved for 24-48 h re-activation was delayed in liver and diminished in heart. The results are discussed with reference to the fate of dietary carbohydrate after re-feeding.

scholarly journals Carbohydrate Metabolism in the Toxoplasma gondii Apicoplast: Localization of Three Glycolytic Isoenzymes, the Single Pyruvate Dehydrogenase Complex, and a Plastid Phosphate Translocator

2007 ◽  
Vol 6 (6) ◽  
pp. 984-996 ◽  
Author(s):  
Tobias Fleige ◽  
Karsten Fischer ◽  
David J. P. Ferguson ◽  
Uwe Gross ◽  
Wolfgang Bohne
Keyword(s):  
Toxoplasma Gondii ◽  
Carbohydrate Metabolism ◽  
Pyruvate Kinase ◽  
Pyruvate Dehydrogenase ◽  
Fusion Proteins ◽  
Pyruvate Dehydrogenase Complex ◽  
Phosphoglycerate Kinase ◽  
Specific Expression ◽  
Phosphate Translocator ◽  
Dehydrogenase Complex

ABSTRACT Many apicomplexan parasites, such as Toxoplasma gondii and Plasmodium species, possess a nonphotosynthetic plastid, referred to as the apicoplast, which is essential for the parasites’ viability and displays characteristics similar to those of nongreen plastids in plants. In this study, we localized several key enzymes of the carbohydrate metabolism of T. gondii to either the apicoplast or the cytosol by engineering parasites which express epitope-tagged fusion proteins. The cytosol contains a complete set of enzymes for glycolysis, which should enable the parasite to metabolize imported glucose into pyruvate. All the glycolytic enzymes, from phosphofructokinase up to pyruvate kinase, are present in the T. gondii genome, as duplicates and isoforms of triose phosphate isomerase, phosphoglycerate kinase, and pyruvate kinase were found to localize to the apicoplast. The mRNA expression levels of all genes with glycolytic products were compared between tachyzoites and bradyzoites; however, a strict bradyzoite-specific expression pattern was observed only for enolase I. The T. gondii genome encodes a single pyruvate dehydrogenase complex, which was located in the apicoplast and absent in the mitochondrion, as shown by targeting of epitope-tagged fusion proteins and by immunolocalization of the native pyruvate dehydrogenase complex. The exchange of metabolites between the cytosol and the apicoplast is likely to be mediated by a phosphate translocator which was localized to the apicoplast. Based on these localization studies, a model is proposed that explains the supply of the apicoplast with ATP and the reduction power, as well as the exchange of metabolites between the cytosol and the apicoplast.

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