scholarly journals The metabolic effects of sodium dichloroacetate in the starved rat

1974 ◽  
Vol 142 (2) ◽  
pp. 279-286 ◽  
Author(s):  
Perry J. Blackshear ◽  
Paul A. H. Holloway ◽  
K. George M. M. Albert
Keyword(s):  
Blood Glucose ◽  
Ketone Body ◽  
Metabolic Effects ◽  
Plasma Insulin Concentration ◽  
Hepatic Glucose ◽  
Extrahepatic Tissues ◽  
Lactate And Pyruvate ◽  
Gluconeogenic Substrates ◽  
Net Release ◽  
Pyruvate Ratio

1. Sodium dichloroacetate (300mg/kg body wt. per h) was infused in 24h-starved rats for 4h. 2. Blood glucose decreased significantly, an effect that had previously only been noted in diabetic animals 3. Plasma insulin concentration decreased by 63% blood lactate and pyruvate concentrations decreased by 50 and 33%, whereas concentrations of 3-hydroxybutyrate and acetoacetate increased by 81 and 73% respectively. 4. Livers were freeze-clamped at the end of the 4h infusion. There were significant decreases in hepatic [glucose], [glucose 6-phosphate], [2-phosphoglycerate], the [lactate]/[pyruvate] ratio, [citrate] and [malate], and also [alanine], [glutamate] and [glutamine], suggesting a diminished supply of gluconeogenic substrates. 5. Animals subjected to a functional hepatectomy at the end of 2h infusions showed no difference in blood-glucose disappearance but a highly significant decrease in the rate of accumulation of lactate, pyruvate, glycerol and alanine, compared with control animals. Dichloroacetate decreased ketone-body clearance. 6. After functional hepatectomy an increase in glutamine accumulation appeared to compensate for the decrease in alanine accumulation. 7. It is concluded that dichloroacetate causes hypoglycaemia by decreasing the net release of gluconeogenic precursors from extrahepatic tissues while inhibiting peripheral ketone-body uptake. 8. These findings are consistent with the activation of pyruvate dehydrogenase (EC 1.2.4.1) in rat muscle by dichloroacetate previously described by Whitehouse & Randle (1973).

Metabolic effects of dobutamine in normal man

1992 ◽  
Vol 82 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Ceri J. Green ◽  
R. S. Frazer ◽  
S. Underhill ◽  
Paula Maycock ◽  
Judith A. Fairhurst ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Glucose ◽  
Glucose Concentration ◽  
Respiratory Exchange Ratio ◽  
Blood Glucose Concentration ◽  
Plasma Potassium ◽  
Metabolic Effects ◽  
Dobutamine Infusion ◽  
Plasma Insulin Concentration ◽  
Placebo Infusion

1. Dobutamine in 5% (w/v) d-glucose was infused at sequential doses of 2, 5 and 10 μg min−1 kg−1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) d-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P<0.001) at 10 μg of dobutamine min−1 kg−1. The respiratory exchange ratio decreased from 0.85 (sem 0.02) before infusion to 0.80 (sem 0.01) at 10 μg of dobutamine min−1 kg−1, but did not alter during the placebo infusion (P> 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of d-glucose alone (P < 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P < 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P < 0.001), and the plasma potassium concentration decreased from 3.8 (sem 0.07) to 3.6 (sem 0.04) mmol/l (P<0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 μg of dobutamine min−1 kg−1 (P<0.001) with no further rise at 10 μg of dobutamine min−1 kg−1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P<0.01). At 10 μg of dobutamine min−1 kg−1, the systolic blood pressure was around 160 mmHg (P < 0.001) and the heart rate was around 92 (sem 8) beats/min compared with 59 (sem 4) beats/min during the placebo infusion (P < 0.001). 6. Dobutamine has metabolic effects. It is markedly thermogenic and lipolytic. It depresses the respiratory exchange ratio and endogenous noradrenaline secretion, stimulates insulin secretion and depresses the blood glucose concentration.

Glycogenolytic substances, hepatic and systemic lactate, and food intake in rats

1984 ◽  
Vol 246 (2) ◽  
pp. R247-R250
Author(s):  
R. Racotta ◽  
M. Islas-Chaires ◽  
C. Vega ◽  
M. Soto-Mora ◽  
M. Russek
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Blood Lactate ◽  
Systemic Blood ◽  
Hepatic Glucose ◽  
Glycogenolytic Effect ◽  
Glucagon And Insulin ◽  
Pyruvate Ratio

Changes in hepatic lactate and glucose and systemic blood lactate produced by intraperitoneal injections of epinephrine, isoproterenol, glucagon, and insulin showed a high correlation (r = 0.9) with the changes in food intake elicited by the same substances. The changes in systemic blood glucose showed no correlation with the changes in feeding, which suggests that central glucoreceptors are not playing an important role in the observed changes in feeding. The intramuscular epinephrine had no significant effect on food intake, in spite of changes in systemic and hepatic lactate and glucose similar to those elicited by intraperitoneal epinephrine. However, intramuscular epinephrine had no hepatic glycogenolytic effect. This suggests that the changes in glucose and lactate elicited by intraperitoneal epinephrine result from hepatic glycogenolysis, whereas the changes elicited by intramuscular epinephrine result from muscular glycogenolysis and inhibition of insulin. Thus hepatic glucose and lactate are good predictors of feeding only when they are produced endogenously by hepatic glycogenolysis. It was concluded that hepatic lactate cannot be the substance sensed by hepatic metabolic receptors. However, due to a possible change in the hepatic lactate-to-pyruvate ratio elicited by intraperitoneal epinephrine, hepatic pyruvate may still be correlated with feeding during the action of both intramuscular and intraperitoneal epinephrine. Therefore the hypothesis that pyruvate is the substance monitored by hepatic metabolic receptors should be tested.

scholarly journals Metabolic interactions of dichloroacetate and insulin in experimental diabetic ketoacidosis. Studies on whole animals and after functional hepatectomy

1975 ◽  
Vol 146 (2) ◽  
pp. 447-456 ◽  
Author(s):  
P J Backshear ◽  
P A H Holloway ◽  
K G M M Alberti
Keyword(s):  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Blood Lactate ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Blood Concentrations ◽  
Metabolic Interactions ◽  
Lactate And Pyruvate ◽  
Body Production ◽  
Body Concentration

1. The infusion of sodium dichloroacetate into rats with severe diabetic ketoacidosis over 4h caused a 2mM decrease in blood glucose, and small falls in blood lactate and pyruvate concentrations. Similar findings had been reported in normal rats (Blackshear et al., 1974). In contrast there was a marked decrease in blood ketone-body concentration in the diabetic ketoacidotic rats after dichloroacetate treatment. 2. The infusion of insulin alone rapidly decreased blood glucose and ketone bodies, but caused an increase in blood lactate and pyruvate. 3. Dichloroacetate did not affect the response to insulin of blood glucose and ketone bodies, but abolished the increase of lactate and pyruvate seen after insulin infusion. 4. Neither insulin nor dichloroacetate stimulated glucose disappearance after functional hepatectomy, but both agents decreased the accumulation in blood of lactate, pyruvate and alanine. 5. Dichloroacetate inhibited 3-hydroxybutyrate uptake by the extra-splachnic tissues; insulin reversed this effect. Ketone-body production must have decreased, as hepatic ketone-body content was unchanged by dicholoracetate yet blood concentrations decreased. 6. It was concluded that: (a) dichloroacetate had qualitatively similar effects on glucose metabolism in severely ketotic rats to those observed in non-diabetic starved animals; (b) insulin and dichloroacetate both separately and together, decreased the net release of lactate, pyruvate and alanine from the extra-splachnic tissues, possibly through a similar mechanism; (c) insulin reversed the inhibition of 3-hydroxybutyrate uptake caused by dichloroacetate; (d) dichloroacetate inhibited ketone-body production in severe ketoacidosis.

Pulsatile hyperglucagonemia fails to increase hepatic glucose production in normal man

1987 ◽  
Vol 252 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
G. Paolisso ◽  
A. J. Scheen ◽  
A. S. Luyckx ◽  
P. J. Lefebvre
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Glucose Infusion ◽  
Metabolic Effects ◽  
Glucose Turnover ◽  
Continuous Administration ◽  
Hepatic Glucose ◽  
Normal Man

To study the metabolic effects of pulsatile glucagon administration, six male volunteers were submitted to a 260-min glucose-controlled glucose intravenous infusion using the Biostator. The endogenous secretion of the pancreatic hormones was inhibited by somatostatin (100 micrograms X h-1), basal insulin secretion was replaced by a continuous insulin infusion (0.2 mU X kg-1 X min-1), and glucagon was infused intravenously in two conditions at random: either continuously (125 ng X min-1) or intermittently (812.5 ng X min-1, with a switching on/off length of 2/11 min). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classical methodology using a D-[3-3H]glucose infusion allowed us to study glucose turnover. While basal plasma glucagon levels were similar in both conditions (122 +/- 31 vs. 115 +/- 18 pg X ml-1), they plateaued at 189 +/- 38 pg X ml-1 during continuous infusion and varied between 95 and 501 pg X ml-1 during pulsatile infusion. When compared with continuous administration, pulsatile glucagon infusion initially induced a similar increase in endogenous (hepatic) glucose production and blood glucose, did not prevent the so-called “evanescent” effect of glucagon on blood glucose, and after 3 h tended to reduce rather than increase hepatic glucose production. In conclusion, in vivo pulsatile hyperglucagonemia in normal man fails to increase hepatic glucose production.

Correlation of Plasma Phenformin Concentration with Metabolic Effects in Normal Subjects

1980 ◽  
Vol 58 (2) ◽  
pp. 153-155 ◽  
Author(s):  
M. Nattrass ◽  
Karen Sizer ◽  
K. G. M. M. Alberti
Keyword(s):  
Blood Glucose ◽  
Plasma Concentration ◽  
Blood Lactate ◽  
Serum Insulin ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Normal Subjects ◽  
Metabolic Effects ◽  
Intermediary Metabolites ◽  
Pyruvate Ratio

1. Circulating concentrations of intermediary metabolites have been measured after administration of 50 mg of phenformin to normal subjects. 2. Phenformin caused a significant increase in blood lactate, alanine and the lactate/pyruvate ratio but did not affect blood glucose or serum insulin concentrations. 3. There was a significant correlation between the increase in blood lactate concentration after phenformin and the plasma concentration of the drug.

Hepatic autoregulation: response of glucose production and gluconeogenesis to increased glycogenolysis

2007 ◽  
Vol 292 (5) ◽  
pp. E1265-E1269 ◽  
Author(s):  
Peter Staehr ◽  
Ole Hother-Nielsen ◽  
Henning Beck-Nielsen ◽  
Michael Roden ◽  
Harald Stingl ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Hepatic Glycogen ◽  
Plasma Insulin Concentration ◽  
Compensatory Response ◽  
Healthy Humans ◽  
Hepatic Glucose ◽  
Glycogen Stores ◽  
Glycogen Formation

The effect of increased glycogenolysis, simulated by galactose's conversion to glucose, on the contribution of gluconeogenesis (GNG) to hepatic glucose production (GP) was determined. The conversion of galactose to glucose is by the same pathway as glycogen's conversion to glucose, i.e., glucose 1-phosphate → glucose 6-phosphate → glucose. Healthy men ( n = 7) were fasted for 44 h. At 40 h, hepatic glycogen stores were depleted. GNG then contributed ∼90% to a GP of ∼8 μmol·kg−1·min−1. Galactose, 9 g/h, was infused over the next 4 h. The contribution of GNG to GP declined from ∼90% to 65%, i.e., by ∼2 μmol·kg−1·min−1. The rate of galactose conversion to blood glucose, measured by labeling the infused galactose with [1-2H]galactose ( n = 4), was also ∼2 μmol·kg−1·min−1. The 41st h GP rose by ∼1.5 μmol·kg−1·min−1 and then returned to ∼9 μmol·kg−1·min−1, while plasma glucose concentration increased from ∼4.5 to 5.3 mM, accompanied by a rise in plasma insulin concentration. Over 50% of the galactose infused was accounted for in blood glucose and hepatic glycogen formation. Thus an increase in the rate of GP via the glycogenolytic pathway resulted in a concomitant decrease in the rate of GP via GNG. While the compensatory response to the galactose administration was not complete, since GP increased, hepatic autoregulation is operative in healthy humans during prolonged fasting.

scholarly journals Uptake and metabolic effects of 3-iodothyronamine in hepatocytes

2014 ◽  
Vol 221 (1) ◽  
pp. 101-110 ◽  
Author(s):  
Sandra Ghelardoni ◽  
Grazia Chiellini ◽  
Sabina Frascarelli ◽  
Alessandro Saba ◽  
Riccardo Zucchi
Keyword(s):  
Hepg2 Cells ◽  
Ketone Body ◽  
Amine Oxidase ◽  
Glucose Production ◽  
Experimental Models ◽  
Oxidase Inhibitor ◽  
Metabolic Effects ◽  
Hormonal Changes ◽  
Hepatic Glucose ◽  
Body Production

3-Iodothyronamine (T1AM) is an endogenous relative of thyroid hormone with profound metabolic effects. In different experimental models, T1AM increased blood glucose, and it is not clear whether this effect is entirely accounted by changes in insulin and/or glucagone secretion. Thus, in the present work, we investigated the uptake of T1AM by hepatocytes, which was compared with the uptake of thyroid hormones, and the effects of T1AM on hepatic glucose and ketone body production. Two different experimental models were used: HepG2 cells and perfused rat liver. Thyronines and thyronamines (T0AMs) were significantly taken up by hepatocytes. In HepG2 cells exposed to 1 μM T1AM, at the steady state, the cellular concentration of T1AM exceeded the medium concentration by six- to eightfold. Similar accumulation occurred with 3,5,3′-triiodothyronine and thyroxine. Liver experiments confirmed significant T1AM uptake. T1AM was partly catabolized and the major catabolites were 3-iodothyroacetic acid (TA1) (in HepG2 cells) and T0AM (in liver). In both preparations, infusion with 1 μM T1AM produced a significant increase in glucose production, if adequate gluconeogenetic substrates were provided. This effect was dampened at higher concentration (10 μM) or in the presence of the amine oxidase inhibitor iproniazid, while TA1 was ineffective, suggesting that T1AM may have a direct gluconeogenetic effect. Ketone body release was significantly increased in liver, while variable results were obtained in HepG2 cells incubated with gluconeogenetic substrates. These findings are consistent with the stimulation of fatty acid catabolism, and a shift of pyruvate toward gluconeogenesis. Notably, these effects are independent from hormonal changes and might have physiological and pathophysiological importance.

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.

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 The mechanism by which adenosine decreases gluconeogenesis from lactate in isolated rat hepatocytes

1987 ◽  
Vol 246 (2) ◽  
pp. 449-454 ◽  
Author(s):  
A Lavoinne ◽  
H A Buc ◽  
S Claeyssens ◽  
M Pinosa ◽  
F Matray
Keyword(s):  
Ketone Body ◽  
Adenine Nucleotides ◽  
Rat Hepatocytes ◽  
Adenosine Kinase ◽  
Isolated Rat Hepatocytes ◽  
Adenosine Deaminase 2 ◽  
Body Production ◽  
Gluconeogenic Substrates ◽  
Isolated Rat ◽  
Stimulation Of

Incubation of hepatocytes from 24 h-starved rats in the presence of 0.5 mM-adenosine decreased gluconeogenesis from lactate, but not from alanine. The inhibition of gluconeogenesis was associated with a stimulation of ketone-body production and an inhibition of pyruvate oxidation. These metabolic changes were suppressed in the presence of iodotubercidin (an inhibitor of adenosine kinase), but were reinforced in the presence of deoxycoformycin (an inhibitor of adenosine deaminase); 2-chloroadenosine induced no change in gluconeogenesis from lactate. These data indicate that the inhibition of gluconeogenesis by adenosine probably results from its conversion into adenine nucleotides. In the presence of lactate or pyruvate, but not with alanine or asparagine, this conversion resulted in a decrease in the [ATP]/[ADP] ratio in both mitochondrial and cytosolic compartments. Adenosine decreased the Pi concentration with all gluconeogenic substrates.

Sign in / Sign up

Export Citation Format

Share Document