Metabolic clearance rate of adrenocorticotropin in the rat

1977 ◽  
Vol 55 (5) ◽  
pp. 1079-1083 ◽  
Author(s):  
Josée Lalonde ◽  
Maurice Normand
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Adrenal Cells ◽  
Acth Concentration ◽  
Acth Release

The metabolic clearance rate (MCR) of adrenocorticotropin (ACTH) was estimated after the intravenous infusion of graded rates of the hormone (40–2560 μU/min per 100 g body weight) in rats pretreated with chlorpromazine, morphine, and Nembutal, a preparation which proved effective in blocking endogenous ACTH release. The hormone was infused over a period of 45 min, at which time the plasma ACTH concentration had reached a steady state. A specific and sensitive bioassay, based on the corticosterone production of dispersed adrenal cells, was used to measure the plasma ACTH concentration. With increasing infusion rates of ACTH, a threefold decrease in the MCR of ACTH was observed. Previous studies of our group have shown that the MCR of corticosterone increases as a function of the infusion rate of the steroid. It appears, therefore, that the metabolism of these two hormonal links of the hypothalarno–pituitary–adrenocortical axis vary in opposite fashions as a function of the secretion rate of the hormone.

Validation of a new method for determination of free fatty acid turnover

1987 ◽  
Vol 252 (3) ◽  
pp. E431-E438 ◽  
Author(s):  
J. M. Miles ◽  
M. G. Ellman ◽  
K. L. McClean ◽  
M. D. Jensen
Keyword(s):  
Steady State ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Clearance Rate ◽  
Experimental Period ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
State Equations ◽  
Tracer Methods

The accuracy of tracer methods for estimating free fatty acid (FFA) rate of appearance (Ra), either under steady-state conditions or under non-steady-state conditions, has not been previously investigated. In the present study, endogenous lipolysis (traced with 14C palmitate) was suppressed in six mongrel dogs with a high-carbohydrate meal 10 h before the experiment, together with infusions of glucose, propranolol, and nicotinic acid during the experimental period. Both steady-state and non-steady-state equations were used to determine oleate Ra ([3H]oleate) before, during, and after a stepwise infusion of an oleic acid emulsion. Palmitate Ra did not change during the experiment. Steady-state equations gave the best estimates of oleate inflow approximately 93% of the known oleate infusion rate overall, while errors in tracer estimates of inflow were obtained when non-steady-state equations were used. The metabolic clearance rate of oleate was inversely related to plasma concentration (P less than 0.01). In conclusion, accurate estimates of FFA inflow were obtained when steady-state equations were used, even under conditions of abrupt and recent changes in Ra. Non-steady-state equations, in contrast, may provide erroneous estimates of inflow. The decrease in metabolic clearance rate during exogenous infusion of oleate suggests that FFA transport may follow second-order kinetics.

scholarly journals Acute Hypoxia Suppresses Exogenous Glucose Rate Of Appearance And Metabolic Clearance Rate During Steady-state Aerobic Exercise

2020 ◽  
Vol 52 (7S) ◽  
pp. 597-597
Author(s):  
Lee M. Margolis ◽  
Marques A. Wilson ◽  
Claire C. Whitney ◽  
Christopher T. Carrigan ◽  
Nancy E. Murphy ◽  
...  
Keyword(s):  
Steady State ◽  
Aerobic Exercise ◽  
Clearance Rate ◽  
Acute Hypoxia ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Exogenous Glucose

Pharmacokinetics and organ-specific metabolism of calcitonin gene-related peptide in sheep

1988 ◽  
Vol 118 (1) ◽  
pp. 25-31 ◽  
Author(s):  
K. G. Braslis ◽  
A. Shulkes ◽  
D. R. Fletcher ◽  
K. J. Hardy
Keyword(s):  
Steady State ◽  
Clearance Rate ◽  
Half Life ◽  
Calcitonin Gene Related Peptide ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Related Peptide ◽  
Modes Of Action ◽  
Calcitonin Gene ◽  
Organ Specific

ABSTRACT Calcitonin gene-related peptide (CGRP) is a product of the calcitonin gene with a widespread distribution in neural tissue of the brain, gut and perivascular nerves. Infusion of CGRP produces multiple biological effects, but the physiological significance of these findings will be influenced by the sites and rates of CGRP metabolism. The metabolic clearance rate and half-life of disappearance of human CGRP were estimated in conscious sheep after infusing CGRP at 1 or 5 pmol/kg per min to steady-state conditions. The particular organs involved in the clearance of CGRP were assessed by measuring the inflow and outflow concentrations across the liver, gut, kidney, lung and brain. The metabolic clearance rate at steady state was 22·6 ± 2·1 (s.e.m.) and 15·0±1·7 ml/kg per min for the 1 and 5 pmol/kg per min doses respectively. The half-life of disappearance was bi-exponential: 3·6±0·3 min for the first phase and 13·6±1·0 min for the second phase. High-pressure liquid chromatography of plasma at equilibrium revealed only a single peak coeluting with CGRP(1–37): no immunoreactive metabolites were detected. These pharmacokinetic values are intermediate between that of a neurotransmitter and a hormone and are therefore consistent for a peptide with both circulatory and neurotransmitter modes of action. The kidney, with an arterial–renal vein gradient of 14%, and the liver, with a portal– hepatic vein gradient of 25%, were the major organs involved in the clearance of CGRP. The specific organ clearance, however, accounted for only one-third of the whole body metabolic clearance rate of CGRP, suggesting that other more generalized degradative systems are involved, such as endothelial-bound enzymes of blood vessels. This information on clearance and organ-specific metabolism should form a basis for evaluating the physiological roles and modes of action of CGRP. J. Endocr. (1988) 118,25–31

Diminished insulin clearance during late pregnancy in patients with Type I diabetes mellitus

1998 ◽  
Vol 95 (3) ◽  
pp. 317-323 ◽  
Author(s):  
Anders O. BJÖRKLUND ◽  
Ulf K. C. ADAMSON ◽  
Per-Eric S. LINS ◽  
L. Magnus R. WESTGREN
Keyword(s):  
Diabetes Mellitus ◽  
Steady State ◽  
Blood Glucose ◽  
Clearance Rate ◽  
Insulin Infusion ◽  
Type I Diabetes ◽  
Type I ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Insulin Levels

1.Intensive insulin treatment of patients with Type I diabetes mellitus during pregnancy is associated with a high frequency of serious hypoglycaemic events. A potential change in insulin metabolism during pregnancy may affect both the frequency and the severity of insulin-induced hypoglycaemia. 2.In 10 patients with Type I diabetes, during the third trimester of pregnancy and 5 to 13 months after delivery, hypoglycaemia was induced by the hyperinsulinaemic hypoglycaemic clamp technique. A constant high-dose intravenous insulin infusion was administered for 150 ;min and arterial blood glucose was clamped at 2.2 ;mmol/l by counterregulation with intravenous glucose. During the experiment venous samples were collected for later analysis of free plasma insulin, whereby the metabolic clearance rate of insulin could be calculated. 3.The desired blood glucose level was approached after approximately 60 ;min of insulin infusion. After just 30 ;min the insulin levels were significantly higher during pregnancy compared with after delivery. In addition, the steady-state insulin level from 90 to 150 ;min was significantly higher during pregnancy. 4.From the steady-state insulin levels at 90 to 150 ;min, the metabolic clearance rate of insulin was calculated, being 24% higher after delivery. 5.We conclude that there is a decreased metabolic clearance rate of insulin during pregnancy. This might be due to altered blood-flow distribution, decreased hepatic insulin extraction and relative increase in body fat during pregnancy. A decreased clearance of insulin will contribute to the risk for serious hypoglycaemic events in patients with Type I diabetes during pregnancy.

Clearance and production of dehydroepiandrosterone and its sulfate in female baboons.

1978 ◽  
Vol 235 (1) ◽  
pp. E74
Author(s):  
H A Schut ◽  
G J Pepe ◽  
J D Townsley
Keyword(s):  
Body Weight ◽  
Clearance Rate ◽  
Secretion Rate ◽  
Metabolic Clearance ◽  
Serum Concentrations ◽  
Human Beings ◽  
Metabolic Clearance Rate ◽  
Lower Serum ◽  
Relative Production ◽  
Secretion Rates

Serum concentrations of dehydroepiandrosterone (D) are greater and those of D sulfate (DS) are lower in female baboons than in women, suggesting interspecies differences in relative production and catabolism of these steroids. To examine this possibility, the metabolic clearance rate (MCR), interconversion (rho), and production of D and DS were determined in five adult female baboons by constant intravenous infusion of [3H]DS and [14C]D. MCR-D (mean +/- SE) was greater (407 +/- 72.8 1/day; 23.1 +/- 3.4 1/day.kg, P less than 0.01) than MCR-DS (44 +/- 5.7 1/day; 2.5 +/- 0.3 1/day.kg). rho-D leads to DS (mean % +/- SE) was greater (45.4 +/- 3.0, P less than 0.001) than rhoDS leads to D (3.8 +/- 0.6), indicating that the equilibrium favors DS formation. Calculated D production and secretion rates were similar (4.5 and 4.4 microgram/min, respectively), whereas DS production (4.1 microgram/min) was twice its secretion rate (2.1 microgram/min). The large difference between MCR-D and MCR-DS resembles that in human beings. However, when clearance is expressed per kilogram body weight, MCR-D is similar to that in man, but MCR-DS is approximately 15-fold greater in the baboon. It is concluded that compared to values in human beings, the greater MCR-DS in baboons maintains the lower serum DS concentration, whereas the higher serum D levels probably result from the relatively greater secretion rate of D baboons.

Constancy and Linearity of the Metabolic Clearance of Adrenocorticotropin in Dogs

1974 ◽  
Vol 52 (1) ◽  
pp. 8-13 ◽  
Author(s):  
John S. Cowan ◽  
Allan E. Davis ◽  
Ross A. Layberry
Keyword(s):  
Metabolic Clearance ◽  
Plasma Samples ◽  
Acth Level ◽  
Turnover Rates ◽  
Metabolic Clearance Rate ◽  
Plasma Acth ◽  
Acth Secretion ◽  
Adrenal Cells ◽  
Dose Dependent ◽  
Versus Concentration

The study of the turnover characteristics of adrenocorticotropin (ACTH) has been facilitated by (1) a sensitive bioassay for ACTH in plasma based upon the response of suspended adrenal cells to ACTH and (2) a technique for preserving the ACTH in small plasma samples. The metabolic clearance rate (MCR) of ACTH was determined by intravenous step infusions of ACTH into dogs lightly anesthetized with Nembutal, without blockade of ACTH secretion; in these dogs the endogenous plasma ACTH level was negligible. The infusion rates ranged from 0.25 to 3.0 mU/kg∙min, yielding plasma ACTH plateau concentrations of 1.8 to 37 mU/100 ml. In no dog did the MCR correlate significantly with plasma concentration, nor did the MCR differ significantly from dog to dog. The 34 successful plateaux yielded a mean MCR of 9.54 ± 0.24 ml/kg∙min. Linear regression of MCR versus concentration yielded a correlation coefficient of −0.00026. The findings showed that the disappearance of ACTH from blood is not dose-dependent and varies negligibly with time or among animals. Hence the measured MCR may be used to convert concentrations of ACTH in plasma into turnover rates.

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.

Elimination of Porcine Secretin in Pigs

1978 ◽  
Vol 54 (1) ◽  
pp. 61-68
Author(s):  
J. Fahrenkrug ◽  
O. B. Schaffalitzky de Muckadell ◽  
J. J. Holst
Keyword(s):  
Whole Blood ◽  
Clearance Rate ◽  
Intravenous Infusion ◽  
Half Life ◽  
Metabolic Clearance ◽  
Distribution Space ◽  
Metabolic Clearance Rate ◽  
The Mean ◽  
Arteriovenous Difference

1. The elimination of immunoreactive secretin was studied in anaesthetized pigs by using constant infusions of pure natural porcine secretin. 2. The mean metabolic clearance rate was 15·4 ml min—1 kg—1, and was independent of the level at which it was determined. The mean distribution space was 64·4 ml/kg. The half-life of secretin after termination of the infusion averaged 2·6 min. 3. During intravenous infusion of secretin in a dose of 27·8 pmol h—1 kg—1 the renal extraction was 52%. Exclusion of the kidneys increased plasma secretin concentration from 26·5 pmol/l to 47·3 pmol/l and increased the half-life to 4·4 min. 4. Exclusion of the liver during infusion of secretin in a dose of 27·8 pmol h—1 kg—1 resulted in an increment in plasma secretin concentration of 7·8 pmol/l and an increase of the half-life to 3·6 min. 5. A gradient of endogenous secretin across the liver was present but no arteriovenous difference was found across the foreleg. 6. Incubation of secretin with whole blood or serum for 20 min at 37°C did not result in any degradation of secretin.

Sign in / Sign up

Export Citation Format

Share Document