Response of ketone body metabolism to exercise during transition from postabsorptive to fasted state

1986 ◽  
Vol 250 (5) ◽  
pp. E495-E501 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Turnover Rate ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Moderate Intensity ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Fasted State ◽  
The Brain

This study examines the effects of a 2-h exercise of moderate intensity (50% of VO2 max) on the tracer-determined turnover rate of ketone bodies (KB) in 21 normal subjects fasted for 16 h, 5 days, whose basal ketonemia ranged between 0.09 and 6.16 mM. The KB response observed at the end of exercise is a function of the initial degree of ketosis. When basal ketonemia is below 0.6 mM, exercise enhances ketogenesis (Ra), the amplitude of this process being positively correlated with KB level. There is a concomitant acceleration of the metabolic clearance rate (MCR) of KB attaining 40-50%. When ketonemia exceeds 2.5 mM, the stimulatory effects of exercise on Ra and on MCR become less marked as basal ketonemia rises and are completely abolished or even reversed when initial KB level is higher than 3-4 mM. The pattern of changes in the concentration and in the overall disposal rate of KB were similar to that of Ra. It is suggested that the parallel inhibition of the stimulatory effect of work on hepatic ketogenesis and on muscular extraction of ketones associated with increasing degrees of fasting hyperketonemia has two physiological implications: it maintains the preferential utilization of KB by nonmuscular tissues (presumably the brain) and prevents the development of uncontrolled hyperketonemia, despite the intense catabolic situation created by the combination of exercise and starvation.

Ketone body turnover during and after exercise in overnight-fasted and starved humans

1983 ◽  
Vol 245 (4) ◽  
pp. E318-E325 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Turnover Rate ◽  
Ketone Bodies ◽  
Sharp Contrast ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Initial Degree ◽  
Stimulation Of ◽  
Marked Drop

The concentration of ketone bodies and their rate of transport (estimated with an infusion of beta-[14C]-hydroxybutyrate) were determined before, during, and after exercise in overnight-fasted and 3- to 5-day-fasted subjects who walked on a treadmill for 2 h at approximately 50% of their VO2max. In overnight-fasted subjects, exercise increased the rate of turnover (+125% after 2 h) and the metabolic clearance rate of ketone bodies whose concentration rose from 0.20 to 0.39 mM. Discontinuation of exercise was associated with a marked increase in ketone levels (+0.73 mM after 30 min of recovery) that was related to a further stimulation of ketogenesis (+19%) and to a marked drop of the metabolic clearance rate to below preexercise values. In sharp contrast with overnight-fasted subjects, starved subjects (with a resting ketone level averaging 5.7 mM) responded to work by a decrease in the turnover rate and in the concentration of ketones, their metabolic clearance rate remaining unchanged. Thus, the response of ketogenesis and muscular ketone uptake to exercise are both markedly influenced by the initial degree of fasting ketosis.

scholarly journals Effect of ischaemic limb injury on the rates of metabolism of ketone bodies in starved rats

1976 ◽  
Vol 156 (2) ◽  
pp. 233-238 ◽  
Author(s):  
R N Barton
Keyword(s):  
Clearance Rate ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Whole Body ◽  
Metabolic Clearance ◽  
O2 Consumption ◽  
Clearance Rates ◽  
Metabolic Clearance Rate ◽  
Limb Injury ◽  
Blood Ketone Bodies

1. Rats starved for 30h were injected with trace amounts of [3-14C]acetoacetate and β-hydroxy[3-14C]butyrate 1h after ischaemic limb injury in a 20 °C environment, and the concentrations and radioactivities of blood ketone bodies were determined at intervals. 2. Starvation alone raised the rates of production and utilization of β-hydroxybutyrate plus acetoacetate about 3.7-fold, but lowered their metabolic clearance rates by about 50%. In the starved rat ketone-body oxidation could account for up to 30% of whole body O2 consumption. 3. Injury in starved rats lowered the rates of production and utilization of both β-hydroxybutyrate and acetoacetate, the combined fall of about 37% slightly exceeding the concomitant fall in whole-body O2 consumption. The concentration of β-hydroxybutyrate decreased after injury, but its metabolic clearance rate was unaltered; the concentration of acetoacetate rose slightly and its metabolic clearance rate fell.

Changes induced by exercise in rates of turnover and oxidation of ketone bodies in fasting man

1978 ◽  
Vol 44 (1) ◽  
pp. 5-11 ◽  
Author(s):  
E. O. Balasse ◽  
F. Fery ◽  
M. A. Neef
Keyword(s):  
Steady State ◽  
Clearance Rate ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Bicycle Ergometer ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Maximal Aerobic Capacity ◽  
Energy Needs

Seven normal subjects fasted for 3 days were exercised for 30 min on a bicycle ergometer at 60 +/- 30% (mean +/- SE) of their maximal aerobic capacity. Rates of transport and oxidation of ketone bodies were determined at rest and during exercise using a primed constant infusion of [14C]acetoacetate. During the initial 7.5 min of exercise, ketone concentration abruptly decreased (-19.4 +/- 3.1%; P less than 0.001) as the result of a 22.2 +/- 7.0% reduction (P less than 0.05) in ketone production rate (Ra) and a 30.4 +/- 7.5% increase (P less than 0.01) in the rate of uptake (Rd) of ketones. As work progressed, blood ketones continued to fall slowly until the 15th min of exercise and thereafter plateaued at a level which was 21.9 +/- 4.1% lower (P less than 0.005) than resting values. During this apparent new steady state, both Ra and Rd were below control values but tended to be equal and to return simultaneously to their preexercise level. The metabolic clearance rate was increased throughout the entire period of exercise, the rise being more marked during the initial 7.5 min (+40.7 +/- 7.5%; P less than 0.01) than at later periods (+19.0 +/- 7.4%; P less than 0.05). Exercise greatly enhanced ketone oxidation which became virtually complete; despite this, the %CO2 derived from ketones, which averaged 17.6 +/- 1.6% at rest, decreased to 10.1 +/- 0.6% (P less than 0.01) after 30 min of work. This indicates that even during the hyperketonemia of fasting, the increased energy needs related to exercise are met primarily by fuels other than ketones.

Stimulatory effect of norepinephrine on ketogenesis in normal and insulin-deficient humans

1984 ◽  
Vol 247 (6) ◽  
pp. E732-E739 ◽  
Author(s):  
U. Keller ◽  
P. P. Gerber ◽  
W. Stauffacher
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Plasma Free Fatty Acid ◽  
Normal Subjects ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance ◽  
Insulin Deficiency ◽  
Norepinephrine Infusion ◽  
Normal Humans ◽  
Body Production

Elevation of plasma norepinephrine concentrations to stress levels (1,800 pg/ml) resulted in normal subjects in a significant increase in ketone body production by 155% (determined by use of [14C]acetoacetate infusions), in a decrease of the metabolic clearance rate by 38%, hyperketonemia, and in increased plasma free fatty acid (FFA) levels by 57% after 75 min. Norepinephrine infusion during somatostatin-induced insulin deficiency resulted in an augmented and sustained increase in ketone body concentrations due to increased production and decreased peripheral clearance of ketone bodies. Norepinephrine's stimulatory effect on lipolysis waned with time, and its effect on ketogenesis in normal subjects was greater than its influence on plasma FFA levels, and thus presumably on hepatic FFA uptake, suggesting a direct stimulatory effect on hepatic ketogenesis. The data demonstrate that in normal humans the hyperketonemic effect of elevated plasma norepinephrine concentrations results from a combination of three factors: increased ketone body production from augmented FFA supply to the liver; accelerated hepatic ketogenesis; and modestly decreased metabolic clearance of ketone bodies. Acute insulin deficiency augments all these effects and results in progressive ketosis.

The Kinetics of Plasma Noradrenaline in Normal and Hypertensive Subjects

1978 ◽  
Vol 55 (s4) ◽  
pp. 89s-92s ◽  
Author(s):  
S. Ghione ◽  
C. Palombo ◽  
M. Pellegrini ◽  
E. Fommei ◽  
A. Pilo ◽  
...  
Keyword(s):  
Clearance Rate ◽  
Normal Subjects ◽  
Plasma Noradrenaline ◽  
Metabolic Clearance ◽  
Venous Sampling ◽  
Metabolic Clearance Rate ◽  
Hypertensive Patients ◽  
Arterial Blood ◽  
Endogenous Noradrenaline ◽  
Kinetics Of

1. The kinetics of plasma noradrenaline have been determined in normal and essential hypertensive patients by intravenous injection of tritiated noradrenaline and serial mixed venous sampling. 2. The metabolic clearance rate of plasma noradrenaline in normal subjects was approximately 1·1 min−1 m−2, whereas in essential hypertensive patients it was significantly reduced to approximately 0·61 min−1 m−2. 3. Metabolic clearance rate was negatively correlated to mean arterial blood pressure and total peripheral resistances. 4. Particularly low values of metabolic clearance rate were found in two patients with congestive heart failure and one with phaeochromocytoma. 5. We propose that the access of plasma noradrenaline to the main removal mechanisms takes place in competition with the flow of unlabelled endogenous noradrenaline directly released by nerve endings. The slower removal of plasma noradrenaline in essential hypertension could then express a larger release of endogenous noradrenaline in this condition.

Metabolic clearance rate of arginine vasopressin in severe chronic renal failure

1992 ◽  
Vol 83 (5) ◽  
pp. 583-587 ◽  
Author(s):  
Nicholas B. Argent ◽  
Robert Wilkinson ◽  
Peter H. Baylis
Keyword(s):  
Renal Failure ◽  
Steady State ◽  
Chronic Renal Failure ◽  
Arginine Vasopressin ◽  
Clearance Rate ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Arginine

1. The metabolic clearance rate of arginine vasopressin was determined using a constant infusion technique in normal subjects and patients with chronic renal failure immediately before commencing dialysis. Endogenous arginine vasopressin was suppressed in all subjects before the infusion with a water load. 2. Plasma arginine vasopressin concentrations were determined using a sensitive and specific radioimmunoassay after Florisil extraction. The detection limit of the assay was 0.3 pmol/l, and intra- and inter-assay coefficients of variation at 2 pmol/l were 9.7% and 15.3%, respectively. 3. In normal subjects, the metabolic clearance rate was determined at two infusion rates producing steady-state concentrations of arginine vasopressin of 1.3 and 4.4 pmol/l. In the patients with renal failure, a single infusion rate was used, producing a steady-state concentration of 1.5 pmol/l. 4. At comparable plasma arginine vasopressin concentrations, metabolic clearance rate was significantly reduced in patients with renal failure (normal 1168 ± 235 ml/min versus renal failure 584 ± 169 ml/min; means ± sd; P<0.001). 5. Free water clearance was significantly reduced in normal subjects during the arginine vasopressin infusion from 8.19 ± 2.61 to −1.41 ± 0.51 ml/min (P<0.001), but was unchanged in the patients with renal failure after attaining comparable plasma arginine vasopressin concentrations. 6. In normal subjects there was a small but significant fall in metabolic clearance rate at the higher steady-state arginine vasopressin concentration (1168 ± 235 ml/min at 1.3 pmol/l versus 1059 ± 269 ml/min at 4.4 pmol/l; P = 0.016). 7. Our results show that the metabolic clearance rate of arginine vasopressin is reduced by approximately 50% in severe chronic renal failure. This alone may account for the raised plasma concentrations of the hormone seen in this condition.

The effect of ketone bodies on leucine and alanine metabolism in dogs

1988 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
A. M. Umpleby ◽  
D. Chubb ◽  
M. A. Boroujerdi ◽  
P. H. Sonksen
Keyword(s):  
Sodium Bicarbonate ◽  
Production Rate ◽  
Clearance Rate ◽  
Ketone Bodies ◽  
Inhibitory Effect ◽  
Leucine Incorporation ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Bicarbonate Infusion ◽  
Alanine Production

1. The effect of an infusion of sodium β-hydroxybutyrate on leucine and alanine metabolism was investigated in dogs starved for 12 h. To determine whether the metabolic changes produced by this infusion were due to the resultant alkalaemia the effect of an equimolar infusion of sodium bicarbonate was also studied. 2. The sodium β-hydroxybutyrate infusion reduced alanine concentration as a result of a decrease in alanine production rate and an increase in alanine metabolic clearance rate. The sodium bicarbonate infusion induced a small decrease in alanine concentration which was due to an increased metabolic clearance rate. Alanine production rate showed no change. This demonstrates that the fall in alanine concentration after a sodium β-hydroxybutyrate infusion is due both to a ketone-specific inhibitory effect on alanine production rate and an increased metabolic clearance rate caused by the alkalaemia. 3. Leucine concentration was increased after the ketone infusion due to a small increase in production rate and there was a small increase in the rate of leucine incorporation into protein. Alkalaemia had no effect on leucine concentration or metabolism.

Metabolism and acid secretory effect of sulfated and nonsulfated gastrin-6 in humans

2000 ◽  
Vol 279 (5) ◽  
pp. G903-G909 ◽  
Author(s):  
C. Palnæs Hansen ◽  
F. Stadil ◽  
J. F. Rehfeld
Keyword(s):  
Clearance Rate ◽  
Main Product ◽  
Acid Output ◽  
Normal Subjects ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Apparent Volume Of Distribution

The antral hormone gastrin is synthesized by processing progastrin into different peptides that stimulate gastric secretion. The effect on acid secretion depends mainly on the metabolic clearance rate of the peptides, but some of them may differ in potency and maximum acid output at similar concentrations in plasma. Sulfated and nonsulfated gastrin-6 are the smallest circulating bioactive gastrins in humans. Their effect and metabolism have now been investigated in nine normal subjects and compared with nonsulfated gastrin-17, a main product of progastrin. Maximum acid output after stimulation with gastrin-17, sulfated gastrin-6, and nonsulfated gastrin-6 were 28.3 ± 2.0, 24.5 ± 2.0 ( P < 0.02), and 19.3 ± 2.3 ( P < 0.05) mmol H+/50 min, respectively, and the corresponding EC50values were 43 ± 6, 24 ± 2 ( P < 0.01), and 25 ± 2 (not significant) pmol/l. The half-life of gastrin-17 was 5.3 ± 0.3 min, the metabolic clearance rate (MCR) was 16.5 ± 1.3 ml · kg−1· min−1, and the apparent volume of distribution (Vd) was 124.3 ± 9.6 ml/kg. The half-lives of sulfated and nonsulfated gastrin-6 were 2.1 ± 0.3 and 1.9 ± 0.3 min, the MCRs were 42.8 ± 3.7 and 139.4 ± 9.6 ml kg−1min−1( P < 0.01), and the Vdwere 139.0 ± 30.5 and 392.0 ± 81.6 ( P < 0.01) ml kg−1. All pharmacokinetic parameters differed significantly from gastrin-17 ( P < 0.01). We conclude that gastrin 6 has a higher potency but a lower efficacy than gastrin-17. The efficacy of gastrin-6 is increased by tyrosine O-sulfation, which also enhances the protection against elimination.

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