scholarly journals Metabolic effects of vasopressin infusion in the starved rat. Reversal of ketonaemia

1983 ◽  
Vol 212 (1) ◽  
pp. 231-239 ◽  
Author(s):  
A M Rofe ◽  
D H Williamson
Keyword(s):  
Plasma Insulin ◽  
Ketone Bodies ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Constant Infusion ◽  
Vasopressin Infusion ◽  
Esterified Fatty Acids ◽  
Lactate And Pyruvate ◽  
Blood Ketone Bodies ◽  
Infusion Regimen

The effects of vasopressin on the metabolism of starved rats were investigated by using a constant-infusion regimen (50 pmol/kg body wt. per min, after an initial loading dose of 150 pmol/kg body wt.). 2. Blood ketone bodies decreased by 50% in 10 min, and this was accompanied by a 60% decrease in the plasma non-esterified fatty acids. 3. Blood glucose increased by 0.9 mM within 5 min and decreased to control values over the 40 min infusion. Small increases in lactate and pyruvate also occurred. 4. Plasma insulin was not increased by vasopressin infusion. 5. The net decrease in blood ketone bodies caused by vasopressin was similar when somatostatin was infused simultaneously (1 nmol/kg body wt. per min). 6. Hepatic ketone bodies were significantly decreased by vasopressin, as was the 3-hydroxybutyrate/acetoacetate ratio. A small increase in the hepatic concentration of several glycolytic intermediates also occurred. 7. Vasopressin did not decrease the ketonaemia produced by infusions of octanoate or long-chain triacylglycerol in rats that had been pre-treated with the anti-lipolytic agent 3,5-dimethylpyrazole. 8. In comparison with vasopressin, the infusion of adrenaline or glucose had much smaller effects in decreasing the ketonaemia of starvation, despite the 4-fold increase in plasma insulin, at 10 min, with the glucose infusion. 9. The primary metabolic effect of vasopressin in the starved rat appears to be that of decreased supply of non-esterified fatty acid to the liver. It is suggested that vasopressin has a direct anti-lipolytic effect in adipose tissue.

scholarly journals Measurement of blood acetoacetate and β-hydroxybutyrate in an automatic analyser

2001 ◽  
Vol 23 (3) ◽  
pp. 69-76 ◽  
Author(s):  
Amparo Galán ◽  
Josém. Hernández ◽  
Orlando Jimenez
Keyword(s):  
Ethylenediaminetetraacetic Acid ◽  
Ketone Bodies ◽  
Mitochondrial Diseases ◽  
Turnaround Time ◽  
Sample Volume ◽  
Intermediary Metabolites ◽  
Transport Chain ◽  
Analytical Response ◽  
Lactate And Pyruvate ◽  
Blood Ketone Bodies

g-hydroxybutyrate and acetoacetate as well as lactate and pyruvate are intermediary metabolites normally present in blood. The g-hydroxybutyrate/acetoacetate ratio is an expression of the mitochondrial oxido-reduction state. This ketone body ratio can provide a clue to diagnosis and metabolic status in congenital errors of the electron transport chain and pyruvate metabolism. The standardization of these analytical procedures improves the interpretation of the results helping in the difficult diagnosis of mitochondrial diseases in children. This study describes an adaptation to a Dimension R 2 L (Dade Behring, Newark, Delaware, USA) automatic analyser for a method to measure blood ketone bodies (g-hydroxybutyrate and acetoacetate). The method allows the metabolites to be measured directly in nondeproteinized plasma (fluoride/ethylenediaminetetraacetic acid). This adaptation simplifies the analytical procedure and limits the turnaround time to 20 minutes. With a sample volume of 200 μ l metabolite concentrations ranging from 12 to 1300 μ molL−1of g-hydroxybutyrate and from 10 to 450 μ molL−1of acetoacetate may be measured with a reliable analytical response.

scholarly journals Mechanism for the ‘anti-lipolytic’ action of vasopressin in the starved rat

1983 ◽  
Vol 212 (3) ◽  
pp. 899-902 ◽  
Author(s):  
A M Rofe ◽  
D H Williamson
Keyword(s):  
Marked Decrease ◽  
Ketone Bodies ◽  
Haemodynamic Effect ◽  
Metabolic Effects ◽  
Fat Depots ◽  
Lipolytic Action ◽  
Esterified Fatty Acids ◽  
Mesenteric Fat ◽  
Flow Through

The marked decrease in blood non-esterified fatty acids and ketone bodies after vasopressin infusion into starved rats [Rofe & Williamson (1983) Biochem. J. 212, 231-239] was investigated. Vasopressin did not inhibit lipolysis in isolated rat adipocytes. The metabolic effects in vivo were still present after pretreatment of rats with indomethacin, indicating that the effect is not secondary to the release of prostaglandins. Vasopressin significantly decreased blood flow through the retroperitoneal, epididymal and mesenteric fat depots, by 80%, 76% and 46% respectively. The specific haemodynamic effect of vasopressin on adipose tissue is considered to be the primary cause of the major metabolic changes seen in the starved rat.

scholarly journals Metabolic effects of propionate in normal and vitamin B12-deficient rats

1971 ◽  
Vol 124 (3) ◽  
pp. 501-507 ◽  
Author(s):  
D. L. Williams ◽  
G. H. Spray ◽  
R. Hems ◽  
D. H. Williamson
Keyword(s):  
Vitamin B12 ◽  
Pyruvate Carboxylase ◽  
Ketone Bodies ◽  
Metabolic Effects ◽  
Acetyl Coa ◽  
Twofold Increase ◽  
Glucose Synthesis ◽  
Lactate And Pyruvate ◽  
Absolute Decrease ◽  
Deficient Group

1. Administration of propionate caused a twofold increase in the concentrations of lactate and pyruvate in the blood of vitamin B12-deficient rats, whereas there was a slight decrease in lactate and a 50% increase in pyruvate in normal rats. 2. Concentrations of total ketone bodies in the blood of normal rats were not significantly altered by propionate administration but the [3-hydroxybutyrate]/[acetoacetate] ratio decreased from 3.0 to 2.0. In the vitamin B12-deficient rats there was a 40% decrease in total ketone bodies and a change in the ratio from 3.4 to 1.2. 3. The changes in the concentration of ketone bodies in freeze-clamped liver preparations were similar in pattern to those observed in blood. 4. Propionate administration caused a decrease in the concentration of acetyl-CoA in the livers of both groups of animals, but the absolute decrease was greater in the vitamin B12-deficient group. The decrease in the concentration of CoA was similar in both groups. 5. As in blood, there were threefold increases in the concentrations of lactate and pyruvate in the livers of the vitamin B12-deficient rats after propionate administration, whereas there was no significant change in the concentrations of these metabolites in the normal rats. 6. There was a 50% inhibition of glucose synthesis in perfused livers from vitamin B12-deficient rats when lactate and propionate were substrates as compared with lactate alone. 7. It is concluded that the conversion of lactate into glucose is inhibited in vitamin B12-deficient rats after propionate administration, and that this effect is due to inhibition of the pyruvate carboxylase step resulting from a decrease in acetyl-CoA concentration and a postulated increase in methylmalonyl-CoA concentration.

Catecholamine responses and their interactions with other glucoregulatory hormones

1984 ◽  
Vol 247 (2) ◽  
pp. E145-E156 ◽  
Author(s):  
M. Vranic ◽  
C. Gauthier ◽  
D. Bilinski ◽  
D. Wasserman ◽  
K. El Tayeb ◽  
...  
Keyword(s):  
Plasma Insulin ◽  
Hepatic Glucose Production ◽  
Severe Hypoglycemia ◽  
Glucose Production ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Epinephrine Infusion ◽  
Hepatic Glucose ◽  
Glucoregulatory Hormones ◽  
Glucagon Suppression

We have investigated catecholamine-glucagon-insulin interactions using three stress models: 1) hypoglycemia; 2) exercise; and 3) epinephrine infusion. Phlorizin caused mild hypoglycemia with hypoinsulinemia. Plasma glucagon increased as did hepatic glucose production. Catecholamines did not increase. Insulin caused severe hypoglycemia. Metabolic counterregulation was due mainly to the 40-fold increase in epinephrine. Glucagon played a role only in the recovery from insulin-induced hypoglycemia, which could reflect increased hepatic sensitivity to glucagon with declining plasma insulin. Glucagon suppression during exercise caused transient hypoglycemia due to an inadequate rise in glucose production. Exaggerated epinephrine release during hypoglycemic exercise prevented severe hypoglycemia by inhibiting glucose utilization and stimulating glucose production, with an associated increase in lactate and free fatty acid levels. Hypoglycemic exercise also caused increased cortisol release. Counterregulation was prevented by a euglycemic clamp. We conclude that, during exercise, glucagon is directly responsible for 80% of the increment of glucose production and controls glucose uptake by the muscle indirectly; thus glucagon spares muscle glycogen by increasing hepatic glucose production. Epinephrine infusion in normal dogs caused a transient increase in glucose production and a sustained inhibition of glucose clearance, resulting in hyperglycemia. Insulin rose transiently, followed by a relative inhibition of secretion. Glucagon suppression did not modify the metabolic effects of epinephrine. In alloxan-diabetic dogs, the glucagon response to epinephrine was augmented, whereas in depancreatized dogs, during subbasal insulin infusion, the hepatic response to glucagon was excessive. Glucagon suppression diminished hepatic responsiveness to epinephrine in both models. Stress-induced diabetic instability could relate to exaggerated glucagon release or to increased hepatic sensitivity to glucagon. Thus, during hypoglycemia, exercise, or epinephrine infusion, prevailing plasma insulin levels govern the relative metabolic roles of epinephrine and glucagon.

Galactose and Hepatic Metabolism in Malnutrition and Sepsis in Man

1978 ◽  
Vol 55 (2) ◽  
pp. 199-204 ◽  
Author(s):  
G. Royle ◽  
M. G. W. Kettlewell ◽  
Vera Ilic ◽  
D. H. Williamson
Keyword(s):  
Blood Glucose ◽  
Metabolic Response ◽  
Ketone Bodies ◽  
Fasting Blood Glucose ◽  
Hepatic Metabolism ◽  
Liver Function Tests ◽  
Lactate And Pyruvate ◽  
Blood Ketone Bodies ◽  
And Function ◽  
Septic Group

1. Hepatic carbohydrate metabolism was studied by an intravenous galactose test in control patients, malnourished non-septic patients, patients with prolonged severe sepsis and patients after recovery from sepsis. 2. Blood galactose half-life was not significantly increased in the septic group despite abnormal liver-function tests, whereas it was approximately doubled in the malnourished patients. 3. The rise in blood glucose after galactose injection was less in both the septic and malnourished groups, as compared with that in the control subjects. 4. Fasting blood glucose, lactate and pyruvate concentrations were similar in all groups, whereas blood ketone bodies were increased in the malnourished and septic groups, and blood alanine was decreased only in the septic group. 5. The changes in hepatic metabolism and function were reversible on recovery from sepsis. 6. It is suggested that alterations in hepatic blood flow and the metabolic fate of galactose within the liver may explain the changes in the metabolic response to galactose observed in malnourished or septic patients.

scholarly journals The development of ketogenesis at birth in the rat

1978 ◽  
Vol 176 (3) ◽  
pp. 759-765 ◽  
Author(s):  
P Ferré ◽  
J P Pégorier ◽  
D H Williamson ◽  
J R Girard
Keyword(s):  
Fatty Acids ◽  
Ketone Bodies ◽  
Liver Glycogen ◽  
Newborn Rat ◽  
Adult Rat ◽  
Rate Limiting Step ◽  
Esterified Fatty Acids ◽  
Major Increase ◽  
Blood Ketone Bodies ◽  
Rate Limiting

In the suckling newborn rat, blood ketone bodies begin to increase slowly 4h after birth and then rise sharply between 12 and 16h, whereas the major increase in plasma non-esterified fatty acids and liver carnitine occurs during the first 2h of life, parallel with the onset of suckling. In the starved newborn rat, which shows no increase in liver carnitine unless it is fed with a carnitine solution, the developmental pattern of the ketogenic capacity (tested by feeding a triacylglycerol emulsion, which increases plasma non-esterified fatty acids by 3-fold) is the same as in the suckling animal. This suggests that the increases in plasma non-esterified fatty acids and liver carnitine seen 2h after birth in the suckling animal are not the predominant factors inducing the switch-on of ketogenesis. Injection of butyrate to starved newborn pups resulted in a pattern of blood ketone bodies which was similar to that found after administration of triacylglycerols, but, at all time points studied, the hyperketonaemia was more pronounced with butyrate. It is suggested that, even if the entry of long-chain fatty acids into the mitochondria is a rate-limiting step, it is not the only factor controlling ketogenesis after birth in the rat. As in the adult rat, there is a reciprocal correlation between the liver glycogen content and the concentration of ketone bodies in the blood.

THE EFFECT OF THE PROGESTOGEN ETHYNODIOL DIACETATE ON GLUCOSE, INSULIN, AND GROWTH HORMONE AFTER SIX MONTHS TREATMENT

1972 ◽  
Vol 70 (2) ◽  
pp. 373-384 ◽  
Author(s):  
W. N. Spellacy ◽  
W. C. Buhi ◽  
S. A. Birk
Keyword(s):  
Growth Hormone ◽  
Blood Glucose ◽  
Plasma Insulin ◽  
Tolerance Test ◽  
Metabolic Effects ◽  
Oral Glucose ◽  
Hormone Levels ◽  
Glucose Levels ◽  
Ethynodiol Diacetate ◽  
Tolerance Curve

ABSTRACT Seventy-one women were treated with a daily dose of 0.25 mg of the progestogen ethynodiol diacetate. They were all tested with a three-hour oral glucose tolerance test before beginning the steroid and then again during the sixth month of use. Measurements were made of blood glucose and plasma insulin and growth hormone levels. There was a significant elevation of the blood glucose levels after steroid treatment as well as a deterioration in the tolerance curve in 12.9% of the women. The plasma insulin values were also elevated after drug treatment whereas the fasting ambulatory growth hormone levels did not significantly change. There was a significant association between the changes in glucose and insulin levels and the subject's age, control weight, or weight gain during treatment. The importance of considering the metabolic effects of the progestogen component of oral contraceptives is stressed.

scholarly journals Effects of peroral alanine administration in lactating ewes with decreased availability of glucose

1997 ◽  
Vol 78 (5) ◽  
pp. 805-813 ◽  
Author(s):  
Kjell Holtenius ◽  
Paul Holtenius
Keyword(s):  
Fatty Acids ◽  
Plasma Level ◽  
Free Fatty Acids ◽  
Skeletal Muscles ◽  
Plasma Insulin ◽  
Glucose Oxidation ◽  
Negative Energy ◽  
Crossover Design ◽  
Metabolic Effects ◽  
Significant Elevation

The metabolic effects of a phlorizin-induced drainage of glucose were studied in six lactating ewes with or without peroral alanine drenches in a study of crossover design. Phlorizin gave rise to a small, but significant, elevation of plasma β-hydroxybutyrate. The plasma level of alanine decreased by about 30 % due to the phlorizin injections and alanine was negatively correlated to β-hydroxybutyrate. The plasma level of free fatty acids increased due to phlorizin. Plasma insulin and glucose concentrations were not significantly affected by phlorizin while glucagon level showed a small but significant increase. Peroral alanine drenches to phlorizin-treated ewes gave rise to a transitory elevation of alanine in plasma. The plasma level of free fatty acids was about 40 % lower in phlorizin-treated ewes receiving alanine and β-hydroxybutyrate tended to be lower (P < 0.08). We suggest that β-hydroxybutyrate, apart from its function as an oxidative fuel, might play an important role by limiting glucose oxidation and protein degradation in skeletal muscles during periods of negative energy balance in ruminants. Furthermore, it is suggested that alanine supplementation decreases lipolysis and ketogenesis in lactating ewes.

scholarly journals Phosphoglycolate has profound metabolic effects but most likely no role in a metabolic DNA response in cancer cell lines

2019 ◽  
Vol 476 (4) ◽  
pp. 629-643 ◽  
Author(s):  
Isabelle Gerin ◽  
Marina Bury ◽  
Francesca Baldin ◽  
Julie Graff ◽  
Emile Van Schaftingen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Lines ◽  
Oxidative Dna Damage ◽  
Fold Increase ◽  
Metabolic Effects ◽  
Phosphoglycerate Mutase ◽  
Wild Type ◽  
Metabolic Disturbances ◽  
Phosphoglycolate Phosphatase ◽  
Damage Repair

Abstract Repair of a certain type of oxidative DNA damage leads to the release of phosphoglycolate, which is an inhibitor of triose phosphate isomerase and is predicted to indirectly inhibit phosphoglycerate mutase activity. Thus, we hypothesized that phosphoglycolate might play a role in a metabolic DNA damage response. Here, we determined how phosphoglycolate is formed in cells, elucidated its effects on cellular metabolism and tested whether DNA damage repair might release sufficient phosphoglycolate to provoke metabolic effects. Phosphoglycolate concentrations were below 5 µM in wild-type U2OS and HCT116 cells and remained unchanged when we inactivated phosphoglycolate phosphatase (PGP), the enzyme that is believed to dephosphorylate phosphoglycolate. Treatment of PGP knockout cell lines with glycolate caused an up to 500-fold increase in phosphoglycolate concentrations, which resulted largely from a side activity of pyruvate kinase. This increase was much higher than in glycolate-treated wild-type cells and was accompanied by metabolite changes consistent with an inhibition of phosphoglycerate mutase, most likely due to the removal of the priming phosphorylation of this enzyme. Surprisingly, we found that phosphoglycolate also inhibits succinate dehydrogenase with a Ki value of <10 µM. Thus, phosphoglycolate can lead to profound metabolic disturbances. In contrast, phosphoglycolate concentrations were not significantly changed when we treated PGP knockout cells with Bleomycin or ionizing radiation, which are known to lead to the release of phosphoglycolate by causing DNA damage. Thus, phosphoglycolate concentrations due to DNA damage are too low to cause major metabolic changes in HCT116 and U2OS cells.

The Removal of Infused Leucine after Injury, Starvation and other Conditions in Man

1980 ◽  
Vol 59 (4) ◽  
pp. 275-283 ◽  
Author(s):  
M. Elia ◽  
Rose Farrell ◽  
Vera Ilic ◽  
R. Smith ◽  
D. H. Williamson
Keyword(s):  
Muscular Dystrophy ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Elective Surgery ◽  
Metabolic Effects ◽  
Accidental Injury ◽  
Sufficient Energy ◽  
Branched Chain ◽  
Clinical Conditions ◽  
Basal Concentration

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal and metabolic effects of infused l-leucine. 2. The blood concentration of leucine was significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy. 3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury. Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis. 4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied. 5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.

Sign in / Sign up

Export Citation Format

Share Document