scholarly journals Stimulation by glucose of gluconeogenesis in hepatocytes isolated from starved rats

1987 ◽  
Vol 245 (3) ◽  
pp. 661-668 ◽  
Author(s):  
M Rigoulet ◽  
X M Leverve ◽  
P J A M Plomp ◽  
A J Meijer
Keyword(s):  
Steady State ◽  
Production Rate ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Carboxylase Activity ◽  
Maximal Stimulation ◽  
Intracellular Concentrations ◽  
Effect Of Glucose ◽  
Stimulation Of

Control properties of the gluconeogenic pathway in hepatocytes isolated from starved rats were studied in the presence of glucose. The following observations were made. (1) Glucose stimulated the rate of glucose production from 20 mM-glycerol, from a mixture of 20 mM-lactate and 2 mM-pyruvate, or from pyruvate alone; no stimulation was observed with 20 mM-alanine or 20 mM-dihydroxyacetone. Maximal stimulation was obtained between 2 and 5 mM-glucose, depending on the conditions. At concentrations above 6 mM, gluconeogenesis declined again, so that at 10 mM-glucose the glucose production rate became equal to that in its absence. (2) With glycerol, stimulation of gluconeogenesis by glucose was accompanied by oxidation of cytosolic NADH and reduction of mitochondrial NAD+ and was insensitive to the transaminase inhibitor amino-oxyacetate; this indicated that glucose accelerated the rate of transport of cytosolic reducing equivalents to the mitochondria via the glycerol 1-phosphate shuttle. (3) With lactate plus pyruvate (10:1) as substrates, stimulation of gluconeogenesis by glucose was almost additive to that obtained with glucagon. From an analysis of the effect of glucose on the curves relating gluconeogenic flux and the steady-state intracellular concentrations of gluconeogenic intermediates under various conditions, in the absence and presence of glucagon, it was concluded that addition of glucose stimulated both phosphoenolpyruvate carboxykinase and pyruvate carboxylase activity.

DDT-Induced Stimulation of Key Gluconeogenic Enzymes In Rat Kidney Cortex

1972 ◽  
Vol 50 (2) ◽  
pp. 225-229 ◽  
Author(s):  
S. Kacew ◽  
R. L. Singhal ◽  
G. M. Ling
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rat Kidney ◽  
Kidney Cortex ◽  
Glucocorticoid Hormones ◽  
Rat Kidney Cortex ◽  
Gluconeogenic Enzymes ◽  
Maximal Stimulation ◽  
Adrenalectomized Rats ◽  
Stimulation Of

Administration of technical DDT or o,p′-DDT produced marked increases in pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glueose-6-phospfaatase activities in rat kidney cortex. Significant increases in these key gluconeogenic enzymes occurred at 2–3 days and maximal stimulation was seen 5–7 days after the beginning of o,p′-DDT treatment. This DDT isomer, when given to adrenalectomized rats, produced increases in renal enzymes similar to those observed in intact animals. Furthermore, since administration of triamcinolone to o,p′-DDT-treated rats failed to potentiate the action of this insecticide on various enzymes, evidence indicates that the stimulation of kidney cortex gluconeogenesis by DDT is not mediated through a release of glucocorticoid hormones from the adrenal cortex.

scholarly journals The characteristics and site of inhibition of gluconeogenesis in rat liver cells by bacterial endotoxin. Stimulation of phosphofructokinase-1

1987 ◽  
Vol 242 (3) ◽  
pp. 721-728 ◽  
Author(s):  
R G Knowles ◽  
J P McCabe ◽  
S J Beevers ◽  
C I Pogson
Keyword(s):  
Enzyme Activities ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Liver Cells ◽  
Atp Content ◽  
Rat Liver Cells ◽  
Endogenous Substrates ◽  
And Control ◽  
Control Coefficients ◽  
Stimulation Of

The characteristics and site of inhibition of gluconeogenesis by endotoxin were investigated in liver cells isolated from control and endotoxin-treated rats. Endotoxin treatment was associated with inhibition (40-50%) of gluconeogenesis from lactate plus pyruvate over a range of concentrations of substrate and of oleate and with or without glucose or glucagon. Similar inhibition was observed with asparagine, proline, glutamine, alanine and a substrate mixture, but not with glycerol, glyceraldehyde, dihydroxyacetone or endogenous substrates. There was no change in cellular ATP content or in the rates of ketogenesis or ureogenesis from asparagine, proline or glutamine. Other effects on isotopic fluxes, metabolite contents, enzyme activities and control coefficients were consistent with the suggestion that the effects of endotoxin on gluconeogenesis are exerted at the level of phosphofructokinase-1, and not at phosphoenolpyruvate carboxykinase, pyruvate kinase, pyruvate carboxylase or glucokinase.

scholarly journals Effect of treatment of rats with dexamethasone in vivo on gluconeogenesis and metabolite compartmentation in subsequently isolated hepatocytes

1984 ◽  
Vol 219 (1) ◽  
pp. 117-123 ◽  
Author(s):  
E H Allan ◽  
M A Titheradge
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Intact Cell ◽  
Isolated Hepatocytes ◽  
Dexamethasone Treatment ◽  
Acetyl Coa ◽  
General Activation ◽  
Effect Of Treatment ◽  
Stimulation Of

Hepatocytes prepared from rats treated with dexamethasone for 2 or 3h and maintained in the presence of 10 microM-dexamethasone in the preparation and incubation buffers showed significantly elevated rates of gluconeogenesis compared with those prepared from control animals. Dexamethasone treatment also increased the sensitivity of the cells to glucagon and the catecholamines. Analysis of the concentrations of metabolites in the gluconeogenic pathway indicated that dexamethasone decreased the intracellular concentration of pyruvate and increased those of phosphoenolpyruvate, acetyl-CoA and citrate, suggesting a stimulation of the reaction(s) converting pyruvate into phosphoenolpyruvate. This was substantiated by analysis of the pattern of metabolites found in the mitochondrial compartment after digitonin fractionation of the cells. Inclusion of 3-mercaptopicolinate in the incubation enhanced the effect of the hormone on the distribution of metabolites. Thus, in the absence of an effect of the steroid at the level of phosphoenolpyruvate carboxykinase or pyruvate kinase, dexamethasone treatment still increased the formation of malate, aspartate and citrate from pyruvate, indicating a stimulation in the intact cell of pyruvate carboxylase. It is suggested that the stimulation of pyruvate carboxylase is a result of a general activation of mitochondrial function, with an increase in the intramitochondrial concentrations of acetyl-CoA and ATP, a decrease in glutamate and an enhanced intramitochondrial [ATP]/[ADP] ratio.

scholarly journals The activities and intracellular distribution of nicotinamide-adenine dinucleotide phosphate-malate dehydrogenase, phosphoenolpyruvate carboxykinase and pyruvate carboxylase in rat, guinea-pig and rabbit tissues

1975 ◽  
Vol 146 (2) ◽  
pp. 329-332 ◽  
Author(s):  
D E Saggerson ◽  
C J Evans
Keyword(s):  
Adipose Tissue ◽  
Guinea Pig ◽  
Malate Dehydrogenase ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Intracellular Distribution ◽  
Kidney Cortex ◽  
Carboxylase Activity ◽  
Liver And Kidney

1. Measurements are presented of the activity and intracellular distribution of phosphoenolypruvate carboxykinase, pyruvate carboxylase and NADP-malate dehydrogenase in rat, guinea-pig and rabbit liver and kidney cortex, together with previously obtained measurements of these enzymes in adipose tissue. 2. In all three tissues pyruvate carboxylase activity was greatest in the rat and lowest in the rabbit. 3. Guinea pig and rabbit were very similar to each other with respect to the extramitochondrial-mitochondrial distribution of phosphoenolpyruvate carboxykinase in all three tissues. 4. NADP-malate dehydrogenase was present in all three tissues in the rat, present in kidney cortex and adipose tissue in the guinea pig and absent from all tissues examines in the rabbit.

scholarly journals Ketone bodies activate gluconeogenesis in isolated rabbit renal cortical tubules incubated in the presence of amino acids and glycerol.

1997 ◽  
Vol 44 (2) ◽  
pp. 323-331 ◽  
Author(s):  
T Lietz ◽  
K Winiarska ◽  
J Bryła
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Kidney Cortex ◽  
Renal Tubules ◽  
Carboxylase Activity ◽  
Glutamate Dehydrogenase Activity ◽  
Glutamine Synthesis ◽  
Glucose Formation ◽  
Stimulation Of

In isolated rabbit renal kidney-cortex tubules 2 mM glycerol, which is a poor gluconeogenic substrate, does not induce glucose formation in the presence of alanine, while it activates gluconeogenesis on substitution of alanine by aspartate, glutamate or proline. The addition of either 5 mM 3-hydroxybutyrate or 5 mM acetoacetate to renal tubules incubated with alanine + glycerol causes a marked induction of glucose production associated with inhibition of glutamine synthesis. In contrast, the rate of the latter process is not altered by ketones in the presence of glycerol and either aspartate, glutamine or proline despite the stimulation of glucose formation. Acceleration of gluconeogenesis by ketone bodies in the presence of amino acids and glycerol is probably due to (i) stimulation of pyruvate carboxylase activity, (ii) activation of malate-aspartate shuttle as concluded from elevated intracellular levels of malate, aspartate and glutamate, as well as (iii) diminished supply of ammonium for glutamine synthesis from alanine resulting from a decrease in glutamate dehydrogenase activity.

scholarly journals The Flavonoid Kaempferol Ameliorates Streptozotocin-Induced Diabetes by Suppressing Hepatic Glucose Production

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2338 ◽  
Author(s):  
Hana Alkhalidy ◽  
Will Moore ◽  
Yao Wang ◽  
Jing Luo ◽  
Ryan McMillan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Pyruvate Carboxylase ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Calorie Intake ◽  
Diabetic Mice ◽  
Insulin Deficiency ◽  
Carboxylase Activity ◽  
Hepatic Glucose ◽  
Streptozotocin Induced Diabetes

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77.8%. This outcome was accompanied by a reduction in hepatic glucose production and an increase in glucose oxidation in the muscle of the diabetic mice, whereas body weight, calorie intake, body composition, and plasma insulin and glucagon levels were not altered. Consistently, treatment with kaempferol restored hexokinase activity in the liver and skeletal muscle of diabetic mice while suppressed hepatic pyruvate carboxylase activity and gluconeogenesis. These results suggest that kaempferol may exert antidiabetic action via promoting glucose metabolism in skeletal muscle and inhibiting gluconeogenesis in the liver.

ENZYMES OF PYRUVATE AND PHOSPHOENOLPYRUVATE CARBOXYLATION IN RUMEN BACTERIA

1974 ◽  
Vol 54 (4) ◽  
pp. 595-603 ◽  
Author(s):  
A. S. ATWAL ◽  
F. D. SAUER
Keyword(s):  
Calcium Phosphate ◽  
Ammonium Sulphate ◽  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Rumen Fluid ◽  
Maximum Activity ◽  
Rumen Bacteria ◽  
Carboxylase Activity ◽  
Mixed Bacteria ◽  
Pep Carboxykinase

Extracts of mixed bacteria collected from bovine rumen fluid contained enzymes that carboxylated pyruvate and phosphoenolpyruvate (PEP). Fresh extracts showed high pyruvate carboxylase activity (EC 6.4.1.1. pyruvate carboxylase) which, however, was cold-labile and lost activity on dialysis at 4 C. Enzyme(s) catalyzing the carboxylation of PEP were stable under these conditions. The carboxylation of PEP was maximally stimulated by ADP and to a lesser degree by GDP. The ADP–requiring PEP carboxykinase [EC 4.1.1.49 phosphoenolpyruvate carboxykinase (ATP)] was equally active with either Mg++ or Mn++ and showed maximum activity at pH 6.5. The GDP–requiring PEP carboxykinase [EC 4.1.1.32 phosphoenolpyruvate carboxykinase (GTP)] required Mn++ and was almost inactive if Mg++ was substituted. Maximum activity was at pH 7.0. These nucleotides were most effective at 2.5-mM concentration and were inhibitory at higher concentrations. In the absence of added ADP or GDP, the carboxylation of PEP continued at a low but persistent rate. Precipitation with ammonium sulphate and adsorption on calcium phosphate gel resulted in fractions containing different proportions of the three activities. These results suggest that in mixed rumen bacterial extracts there are four separate enzymes capable of synthesizing oxaloacetate: one that catalyzes the carboxylation of pyruvate and three that catalyze the carboxylation of PEP.

scholarly journals Receptor-operated Ca2+ channels in gastric parietal cells: gastrin and carbachol induce Ca2+ influx in depleting intracellular Ca2+ stores

1993 ◽  
Vol 289 (1) ◽  
pp. 117-124 ◽  
Author(s):  
S Roche ◽  
J P Bali ◽  
R Magous
Keyword(s):  
Steady State ◽  
Receptor Activation ◽  
Parietal Cells ◽  
The Other ◽  
Bivalent Cation ◽  
Gtp Binding ◽  
Gastric Parietal Cells ◽  
Type Receptor ◽  
Ca2 Channels ◽  
Stimulation Of

The mechanism whereby gastrin-type receptor and muscarinic M3-type receptor regulate free intracellular Ca2+ concentration ([Ca2+]i) was studied in rabbit gastric parietal cells stimulated by either gastrin or carbachol. Both agonists induced a biphasic [Ca2+]i response: a transient [Ca2+]i rise, followed by a sustained steady state depending on extracellular Ca2+. Gastrin and carbachol also caused a rapid and transient increase in Mn2+ influx (a tracer for bivalent-cation entry). Pre-stimulation of cells with one agonist drastically decreased both [Ca2+]i increase and Mn2+ influx induced by the other. Neither diltiazem nor pertussistoxin treatment had any effect on agonist-stimulated Mn2+ entry. Thapsigargin, a Ca(2+)-pump inhibitor, induced a biphasic [Ca2+]i increase, and enhanced the rate of Mn2+ entry. Preincubation of cells with thapsigargin inhibits the [Ca2+]i increase as well as Mn2+ entry stimulated by gastrin or by carbachol. Thapsigargin induced a weak but significant increase in Ins(1,4,5)P3 content, but this agent had no effect on the agonist-evoked Ins(1,4,5)P3 response. In permeabilized parietal cells, Ins(1,4,5)P3 and caffeine caused an immediate Ca2+ release from intracellular pools, followed by a reloading of Ca2+ pools which can be prevented in the presence of thapsigargin. We conclude that (i) gastrin and carbachol mobilize common Ca2+ intracellular stores, (ii) Ca2+ permeability secondary to receptor activation involves neither a voltage-sensitive Ca2+ channel nor a GTP-binding protein from the G1 family, and (iii) agonists regulate common Ca2+ channels in depleting intracellular Ca2+ stores.

Induction of renal phosphoenolpyruvate carboxykinase mRNA: suppressive effect of glucose

1989 ◽  
Vol 257 (1) ◽  
pp. F145-F151
Author(s):  
A. S. Pollock
Keyword(s):  
Metabolic Acidosis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Suppressive Effect ◽  
Oral Glucose ◽  
Prolonged Fasting ◽  
Glucose Loading ◽  
Glucose Administration ◽  
Liver And Kidney ◽  
Gluconeogenic Enzyme ◽  
Effect Of Glucose

The mRNA for the important gluconeogenic enzyme phosphoenolpyruvate carboxykinase (GTP) (PEPCK; EC 4.1.1.32) is expressed in liver and kidney. In the kidney, acidosis is a unique and potent stimulus, whereas insulin, the major counterregulatory hormone of gluconeogenesis, has no effect. In this study, we find that oral glucose administration to rats rapidly decreases the abundance of renal PEPCK mRNA by 50–72%. This reduction takes place in normal euglycemic, in insulin-induced hypoglycemic, and in streptozotocin-induced hyperglycemic diabetic animals. The effect of glucose is not seen in the presence of metabolic acidosis, whether induced by NH4Cl or by prolonged fasting. Therefore, it appears that oral glucose loading is a physiological suppressor of renal PEPCK message abundance, although not in acidosis.

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