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

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.

1986 ◽  
Vol 250 (5) ◽  
pp. E495-E501 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse

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.


1983 ◽  
Vol 245 (4) ◽  
pp. E318-E325 ◽  
Author(s):  
F. Fery ◽  
E. O. Balasse

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.


1973 ◽  
Vol 56 (2) ◽  
pp. 285-294 ◽  
Author(s):  
B. A. PANARETTO ◽  
J. Y. F. PATERSON ◽  
F. HILLS

SUMMARY The uptake of cortisol by organs in the splanchnic area of conscious, undisturbed sheep was estimated before and during the administration of adrenocorticotrophic hormone (ACTH) by measuring cortisol concentration differences in portal and hepatic venous plasma and estimating hepatic plasma flow rates. Metabolic clearance rates (MCR) of plasma cortisol were measured simultaneously. The total splanchnic clearance of cortisol was 61% of MCR in the animal, 48% being accounted for by the liver. When ACTH was given there were increases in MCR and these were accompanied by proportional increases in hepatic plasma flow rates. When ACTH was infused the total splanchnic clearance rate was 65% of MCR, 52–59% being accounted for by the liver. In other experiments the renal clearance rate of cortisol was studied. Under control conditions, and when ACTH was given, the renal clearance was 11% of MCR. The relationship of the sum of individual clearances to MCR is compared and discussed.


1967 ◽  
Vol 39 (3) ◽  
pp. 395-403 ◽  
Author(s):  
D. Y. WANG ◽  
R. D. BULBROOK ◽  
F. ELLIS ◽  
M. M. COOMBS

SUMMARY The metabolic clearance rates, distribution volumes and half-lives of pregnenolone, 17-acetoxypregnenolone and their sulphate esters were determined in man and in the rabbit. Pregnenolone was cleared about three times more quickly than pregnenolone sulphate in both species. The metabolic clearance rate of 17-acetoxypregnenolone sulphate is greater in the rabbit than in man, whether expressed in absolute terms or in relation to the metabolic clearance rate of the free steroid. The slow clearance rate of 17-acetoxypregnenolone sulphate in man is similar to that of testosterone sulphate, dehydroepiandrosterone sulphate and cholesterol sulphate; but is unlike that of pregnenolone sulphate, which is cleared approximately ten times as quickly.


1967 ◽  
Vol 38 (3) ◽  
pp. 307-318 ◽  
Author(s):  
D. Y. WANG ◽  
R. D. BULBROOK ◽  
A. SNEDDON ◽  
T. HAMILTON

SUMMARY The disappearance of isotopically labelled dehydroepiandrosterone, testosterone and their sulphates from the peripheral circulation of man, rabbit and rat has been investigated. Metabolic clearance rates, distribution volumes and half-lives have been determined for these compounds in the above species. In man, the steroid sulphates have a much lower metabolic clearance rate than the corresponding free steroids. This large difference stems from longer half-lives and lower distribution volumes of the former. In the rabbit or rat the steroid sulphates and the appropriate free steroids do not show such marked differences in their metabolic clearance rates: the half-lives and distribution volumes are comparable.


1980 ◽  
Vol 86 (2) ◽  
pp. 363-370 ◽  
Author(s):  
R. N. BARTON ◽  
B. J. PASSINGHAM

Bilateral hind-limb ischaemia in the rat is known to cause insulin resistance, as shown by a sustained rise in plasma glucose concentration with a decreased metabolic clearance rate but no fall in plasma insulin. However, when the concomitant rise in the plasma concentration of corticosterone was diminished by an inhibitor of its biosynthesis, trilostane (WIN 24 540), the hyperglycaemia became transient. The mechanism of this effect has now been studied by measuring the rate of disappearance of [5-3H,U-14C]glucose and the concentration of insulin in plasma. Trilostane did not alter the rate of glucose production or the 3H: 14C ratio (an index of recycling through gluconeogenic precursors). It did, however, raise the metabolic clearance rate while lowering the plasma insulin concentration, i.e. peripheral sensitivity and/or responsiveness to insulin was increased. Insulin resistance was restored by giving corticosterone together with trilostane. Thus an increased concentration of corticosterone in the plasma was necessary for the full development of insulin resistance following ischaemic limb injury. It was, however, probably not the only factor since a similar dose of corticosterone did not lead to hyperglycaemia in uninjured rats.


1988 ◽  
Vol 74 (1) ◽  
pp. 41-48 ◽  
Author(s):  
A. M. Umpleby ◽  
D. Chubb ◽  
M. A. Boroujerdi ◽  
P. H. Sonksen

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.


1978 ◽  
Vol 44 (1) ◽  
pp. 5-11 ◽  
Author(s):  
E. O. Balasse ◽  
F. Fery ◽  
M. A. Neef

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.


1993 ◽  
Vol 5 (2) ◽  
pp. 181 ◽  
Author(s):  
DJ Phillips ◽  
NL Hudson ◽  
S Lun ◽  
LA Condell ◽  
KP McNatty

Five pituitary preparations of follicle stimulating hormone (FSH), namely NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P., were examined for biological activity in terms of their potency in an in vitro bioassay, receptor assay and heterologous radioimmunoassay and in terms of their metabolic clearance rates. In the three assays, Bioscan oFSH was the most potent (P < 0.05) (3- to 5-fold the potency of NIDDK-oFSH-17), with Ovagen being 25-50% the potency of the NIDDK standard (P < 0.05). Folltropin-V and F.S.H.-P. had the lowest potencies in all three assays. For each preparation, the ratio of activities between the assays was not consistent, suggesting that the preparations behaved differently in each assay. In 9 of 10 cases, potency estimates in the heterologous radioimmunoassay were greater than those in the in vitro bioassay or receptor assay. Polyacrylamide gel electrophoresis of the preparations showed banding consistent with the molecular weight of FSH, but also indicated that the preparations were contaminated with other proteins to varying extents. The half-lives of these preparations when injected into the bloodstream of mature female mice were 28.0, 8.6, 13.4, 11.6 and 17.4 min for NIDDK-oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P. respectively. The slopes of the decay rates were significantly different from each other (P < 0.05) except between Ovagen and Folltropin-V. The results of these studies show that a number of widely available FSH preparations have differing biopotencies. Moreover, the biopotency of a preparation in vitro is not related to its metabolic clearance rate, and not all FSH preparations behave identically in different assays. Measures of biopotency in vitro combined with those of metabolic clearance rate may provide useful information on the properties of FSH preparations used for research purposes and for superovulation of farmed livestock.


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