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.

Plasma glucose concentration determines direct versus indirect liver glycogen synthesis

1986 ◽  
Vol 251 (5) ◽  
pp. E584-E590 ◽  
Author(s):  
C. H. Lang ◽  
G. J. Bagby ◽  
H. L. Blakesley ◽  
J. L. Johnson ◽  
J. J. Spitzer
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Infusion Rate ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Glucose Infusion ◽  
Glucose Infusion Rate ◽  
Hepatic Glycogen ◽  
Glucose Load ◽  
Indirect Pathway

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.

Effect of enteral vs. parenteral glucose delivery on initial splanchnic glucose uptake in nondiabetic humans

2002 ◽  
Vol 283 (2) ◽  
pp. E259-E266 ◽  
Author(s):  
Adrian Vella ◽  
Pankaj Shah ◽  
Rita Basu ◽  
Ananda Basu ◽  
Michael Camilleri ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Glucose Disappearance ◽  
Glucose Flux ◽  
Acetaminophen Glucuronide

To determine if enteral delivery of glucose influences splanchnic glucose metabolism, 10 subjects were studied when glucose was either infused into the duodenum at a rate of 22 μmol · kg−1 · min−1 and supplemental glucose given intravenously or when all glucose was infused intravenously while saline was infused intraduodenally. Hormone secretion was inhibited with somatostatin, and glucose (∼8.5 mmol/l) and insulin (∼450 pmol/l) were maintained at constant but elevated levels. Intravenously infused [6,6-2H2]glucose was used to trace the systemic appearance of intraduodenally infused [3-3H]glucose, whereas UDP-glucose flux (an index of hepatic glycogen synthesis) was measured using the acetaminophen glucuronide method. Despite differences in the route of glucose delivery, glucose production (3.5 ± 1.0 vs. 3.3 ± 1.0 μmol · kg−1 · min−1) and glucose disappearance (78.9 ± 5.7 vs. 85.0 ± 7.2 μmol · kg−1 · min−1) were comparable on intraduodenal and intravenous study days. Initial splanchnic glucose extraction (17.5 ± 4.4 vs. 14.5 ± 2.9%) and hepatic UDP-glucose flux (9.0 ± 2.0 vs. 10.3 ± 1.5 μmol · kg−1 · min−1) also did not differ on the intraduodenal and intravenous study days. These data argue against the existence of an “enteric” factor that directly (i.e., independently of circulating hormone concentrations) enhances splanchnic glucose uptake or hepatic glycogen synthesis in nondiabetic humans.

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.

Glycogen Synthesis in Rat Liver from a Pool of Free Glucose

1993 ◽  
Vol 48 (1-2) ◽  
pp. 85-91 ◽  
Author(s):  
H. Schimassek ◽  
Ingrid Meißner
Keyword(s):  
Glycogen Synthesis ◽  
Specific Radioactivity ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Enzyme Complex ◽  
Indirect Pathway ◽  
Free Glucose ◽  
Complex Subject

Glycogen synthesis in isolated perfused livers or livers of anesthetized rats (in situ), was studied using radioactively labelled fructose, lactate, and inositol as substrates. The specific radioactivity of glucose and glycogen was measured at various times and compared with that of some intermediates. The results suggest that liver glycogen is formed from the pool of free glucose which in turn is fed by the so-called “direct and indirect pathway” of glycogen synthesis. This points to an important role of glucose-6-phosphatase, an enzyme complex subject to regulation by glucocorticoids, well known promoters of hepatic glycogen synthesis.

scholarly journals Effects of Meal Fructose/Glucose Composition on Postprandial Glucose Appearance and Hepatic Glycogen Synthesis in Healthy Subjects

2021 ◽  
Vol 10 (4) ◽  
pp. 596
Author(s):  
Cristina Barosa ◽  
Rogério T. Ribeiro ◽  
Rita Andrade ◽  
João F. Raposo ◽  
John G. Jones
Keyword(s):  
Plasma Glucose ◽  
Healthy Subjects ◽  
Glycogen Synthesis ◽  
Krebs Cycle ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Metabolic Complications ◽  
Glucose Ratio ◽  
Dietary Fructose ◽  
P Sources

Dietary fructose overshadows glucose in promoting metabolic complications. Intestinal fructose metabolism (IFM) protects against these effects in rodents, by favoring gluconeogenesis, but the extent of IFM in humans is not known. We therefore aimed to infer the extent of IFM by comparing the contribution of dietary fructose to systemic glucose and hepatic glycogen appearance postprandially. Twelve fasting healthy subjects ingested two protein meals in random order, one supplemented with 50 g 5/95 fructose/glucose (LF) and the other with 50 g 55/45 fructose/glucose (HF). Sources of postprandial plasma glucose appearance and hepatic glycogen synthesis were determined with deuterated water. Plasma glucose excursions, as well as pre- and post-meal insulin, c-peptide, and triglyceride levels were nearly identical for both meals. The total gluconeogenic contribution to plasma glucose appearance was significantly higher for HF versus LF (65 ± 2% vs. 34 ± 3%, p < 0.001). For HF, Krebs cycle anaplerosis accounted for two-thirds of total gluconeogenesis (43 ± 2%) with one-third from Triose-P sources (22 ± 1%). With LF, three-quarters of the total gluconeogenic contribution originated via Krebs cycle anaplerosis (26 ± 2%) with one-quarter from Triose-P sources (9 ± 2%). HF and LF gave similar direct and indirect pathway contributions to hepatic glycogen synthesis. Increasing the fructose/glucose ratio had significant effects on glucose appearance sources but no effects on hepatic glycogen synthesis sources, consistent with extensive IFM. The majority of fructose carbons were converted to glucose via the Krebs cycle.

Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man

1992 ◽  
Vol 83 (6) ◽  
pp. 677-682
Author(s):  
R. F. G. J. King ◽  
M. Madan ◽  
D. Alexander ◽  
A. Boyd ◽  
K. Ibrahim ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Human Liver ◽  
Glycogen Synthesis ◽  
Hepatic Glycogen ◽  
Indirect Pathway ◽  
Abdominal Operation ◽  
Direct Pathway ◽  
Specific Activities ◽  
Glycogen Repletion ◽  
Indirect Route

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the ‘indirect’ pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the ‘direct’ pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7–74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.

Effect of fasting on the intracellular metabolic partition of intravenously infused glucose in humans

1999 ◽  
Vol 277 (5) ◽  
pp. E815-E823 ◽  
Author(s):  
F. Fery ◽  
L. Plat ◽  
E. O. Balasse
Keyword(s):  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Normal Subjects ◽  
Glucose Disposal ◽  
Indirect Pathway ◽  
Total Carbohydrate ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Direct Pathway ◽  
Group 3 ◽  
Group 2

The effects of fasting on the pathways of insulin-stimulated glucose disposal were explored in three groups of seven normal subjects. Group 1 was submitted to a euglycemic hyperinsulinemic clamp (∼100 μU/ml) after both a 12-h and a 4-day fast. The combined use of [3-3H]- and [U-14C]glucose allowed us to demonstrate that fasting inhibits, by ∼50%, glucose disposal, glycolysis, glucose oxidation, and glycogen synthesis via the direct pathway. In group 2, in which the clamp glucose disposal during fasting was restored by hyperglycemia (155 ± 15 mg/dl), fasting stimulated glycogen synthesis (+29 ± 2%) and inhibited glycolysis (−32 ± 3%) but only in its oxidative component (−40 ± 3%). Results were similar in group 3 in which the clamp glucose disposal was restored by a pharmacological elevation of insulin (∼2,800 μU/ml), but in this case, both glycogen synthesis and nonoxidative glycolysis participated in the rise in nonoxidative glucose disposal. In all groups, the reduction in total carbohydrate oxidation (indirect calorimetry) induced by fasting markedly exceeded the reduction in circulating glucose oxidation, suggesting that fasting also inhibits intracellular glycogen oxidation. Thus prior fasting favors glycogen retention by three mechanisms: 1) stimulation of glycogen synthesis via the direct pathway; 2) preferential inhibition of oxidative rather than nonoxidative glycolysis, thus allowing carbon conservation for glycogen synthesis via the indirect pathway; and 3) suppression of intracellular glycogen oxidation.

Mechanism of delayed hepatic glycogen synthesis after an oral galactose load vs. an oral glucose load in adult rats

1992 ◽  
Vol 263 (1) ◽  
pp. E42-E49 ◽  
Author(s):  
C. B. Niewoehner ◽  
B. Neil
Keyword(s):  
Glucose Concentration ◽  
Glycogen Synthesis ◽  
Liver Glycogen ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Glucose Load ◽  
Adult Rats ◽  
Glycogen Accumulation ◽  
Glucose Administration

We have compared the effects of administration of oral galactose or glucose (1 g/kg) to 24-h fasted rats to examine the mechanism by which galactose regulates its own incorporation into liver glycogen in vivo. Liver glycogen increased to a maximum more slowly after galactose than after glucose administration (0.14 vs. 0.29 mumol.g liver-1.min-1). Glycogen accumulation after the galactose load was 70% of that after the glucose load (149 vs. 214 mumol), and the net increase in liver glycogen represented the same proportion (24 vs. 22%) of added carbohydrate after urinary loss of galactose was accounted for. Slower glycogen accumulation after galactose vs. glucose loading could not be explained by galactosuria, by differences in the active forms of synthase or phosphorylase, by end product (glycogen) inhibition of synthase phosphatase, or by different concentrations of the known allosteric effectors of synthase R plus I and phosphorylase a. Similar increases in glucose 6-phosphate were observed after both hexoses. AMP and ADP increased only transiently after galactose administration, and ATP, UTP, and Pi concentrations were unchanged. The UDP-glucose concentration decreased, whereas the UDP-galactose concentration increased two- to threefold after galactose but not glucose administration. The UDP-glucose pyrophosphorylase reaction is inhibited competitively by UDP-galactose. This could explain the decreased UDP-glucose concentration and the reduced rate of glycogen synthesis after galactose was given.

Evaluation of hepatic glycogen content, some haematological and biochemical parameters of alloxan-induced diabetic rats treated with combinations of glibenclamide and G. latifolium extract

2017 ◽  
Vol 14 (4) ◽  
Author(s):  
Patrick E. Aba
Keyword(s):  
Glycogen Content ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Control Groups ◽  
Group 4 ◽  
Male Wistar Rats ◽  
The Mean ◽  
Group 2 ◽  
Alloxan Monohydrate ◽  
Group 1

AbstractBackgroundDiabetes is associated with both biochemical and haematological complications. Combination therapy has been advocated to mitigate some of these complications.AimThis study was designed to investigate the effects of glibenclamide andMethodsThirty male Wistar rats were assigned into five groups of six rats each. Groups 2–5 rats received intraperitoneally, 160 mg/kg of alloxan monohydrate while group 1 rats served as normal control. Groups 2–5 rats were respectively treated with 10 mL/kg distilled water (DW), 2 mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL, while group 1 rats received 10 mL/kg DW. All treatments wereResultsCreatinine and BUN values of groups 3 and 4 rats were comparable to that of group 1 but were significantly (p<0.05) lower when compared with those of groups 2 and 5. There were significant (p<0.05) increases in the mean hepatic glycogen content, RBC, PCV, and Hb of group 4 rats when compared to those of group 2.ConclusionsIt was concluded that a combination of glibenclamide and

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