Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs

1984 ◽  
Vol 246 (1) ◽  
pp. E14-E20
Author(s):  
P. Vaitkus ◽  
A. Sirek ◽  
K. H. Norwich ◽  
O. V. Sirek ◽  
R. H. Unger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Venous Blood ◽  
Compartment Model ◽  
Glucose Turnover ◽  
Base Line ◽  
Indwelling Catheter ◽  
Two Compartment Model ◽  
Portal Venous Blood ◽  
Glucose Output

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

The effects of amino acid supply on the sensitivity of IGF-1 secretion to growth hormone stimulation in ovine hepatocytes

1999 ◽  
Vol 1999 ◽  
pp. 160-160
Author(s):  
N.M. Wheelhouse ◽  
D.G. Hazlerigg ◽  
J.C. MacRae ◽  
M.A. Lomax
Keyword(s):  
Growth Hormone ◽  
Amino Acid ◽  
Venous Blood ◽  
Tissue Growth ◽  
Portal Venous Blood ◽  
Protein Supply ◽  
Amino Acid Concentrations ◽  
Blood Data

Many of the anabolic effects of growth hormone (GH), including promotion of lean tissue growth, are mediated by the actions of insulin-like growth factor-1 (IGF-1) (Gluckman et al, 1987). It is known that the response of hepatic IGF-1 synthesis to GH may be modulated by alterations in levels of feeding or changes in protein supply (Pell et al, 1993). The aim of the current study was to develop an in vitro model to characterise interactions between amino acid supply and GH on hepatic IGF-1 release in ruminants.Ovine hepatocyes were prepared by a modification of a published method (Luo et al, 1992) from the median lobe of livers removed immediately after slaughter from sheep killed at a local abattoir. Free amino acid concentrations in test media were 5x, 1x and 0.2x physiological concentrations based upon in vivo ovine portal venous blood data (Lobley et al, 1995).

Estimation of the rate of appearance in the non-steady state with a two-compartment model

1992 ◽  
Vol 263 (2) ◽  
pp. E400-E415 ◽  
Author(s):  
A. Mari
Keyword(s):  
Steady State ◽  
Time Course ◽  
Specific Activity ◽  
Glucose Production ◽  
Compartment Model ◽  
New Method ◽  
Two Compartment Model ◽  
Glucose Clamp Technique ◽  
Glucose Output ◽  
The Relationship

A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two-compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis.

scholarly journals Intestinal Permeability Assays: a Review

2021 ◽  
Vol 31 (1) ◽  
pp. 20-30
Author(s):  
A. A. Iakupova ◽  
S. R. Abdulkhakov ◽  
R. K. Zalyalov ◽  
A. G. Safin ◽  
R. A. Abdulkhakov
Keyword(s):  
Intestinal Permeability ◽  
Ex Vivo ◽  
Venous Blood ◽  
Intestinal Barrier ◽  
Intestinal Lumen ◽  
Alcoholic Fatty Liver ◽  
Key Points ◽  
Assessment Techniques ◽  
Portal Venous Blood

Aim. A literature review of intestinal permeability assessment techniques.Key points. The intestinal barrier is a functional entity separating the intestinal lumen and internal body, and intestinal permeability is a measure of the barrier functionality. The intestinal barrier integrity and permeability assays differ by the application setting (in vivo or ex vivo), subject (human or animal), marker molecules used to assess permeability (ions, various size carbohydrates, macromolecules, antigens, bacterial products and bacteria), biomaterial for the marker concentration assays (peripheral blood, portal venous blood, urine, stool). Despite a great variety of methods for assessing intestinal permeability, their clinical application requires further studies due to a lack of standardisation, the complexity of selected techniques and occasional limited reliability of results.Conclusion. Further investigation and improvement of intestinal permeability assays is required. The assay and result standardisation will facilitate practice in functional and organic intestinal diseases, as well as allergies, diabetes mellitus, non-alcoholic fatty liver disease and some other illnesses.

Periodic interactions of GH-releasing factor and somatostatin can augment GH release in vitro

1987 ◽  
Vol 253 (5) ◽  
pp. E508-E514
Author(s):  
J. Weiss ◽  
M. J. Cronin ◽  
M. O. Thorner
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Male Rat ◽  
Base Line ◽  
Additive Effects ◽  
Growth Hormone Releasing Factor ◽  
The Impact

Growth hormone (GH) is secreted as pulses in vivo. To understand the signals governing this periodicity, we have established a perifusion-based model of pulsatile GH release. Male rat anterior pituitaries were dispersed and perifused with pulses of human growth hormone-releasing factor-(1--40) (GHRF), with or without a continuous or discontinuous somatostatin tonus. An experiment was composed of a 1-h base-line collection followed by four 3-h cycles; each contained single or paired 10-min infusion(s) of 3 nM GHRF. In testing the impact of somatostatin, the protocol was identical except that 0.3 nM somatostatin was added 30 min into the base-line period and then was either continued throughout the study or withdrawn during the periods of GHRF infusion. GH base lines with somatostatin were lower than vehicle base lines (P less than 0.05). GHRF pulses generated consistent peaks of GH release between 200 and 300 ng. min-1. (10(7) cells)-1, and these peaks were not altered by continuous somatostatin. In contrast, withdrawal of somatostatin during GHRF administration elicited markedly higher GH peaks (P less than 0.05) and more total GH release (P less than 0.05). This response could not be accounted for by the additive effects of GHRF and somatostatin withdrawal.

Kinetics of transepithelial movement of heavy metals in rat jejunum

1987 ◽  
Vol 253 (2) ◽  
pp. G134-G138
Author(s):  
E. C. Foulkes ◽  
D. M. McMullen
Keyword(s):  
Heavy Metals ◽  
Venous Blood ◽  
Compartment Model ◽  
Intestinal Lumen ◽  
Rat Jejunum ◽  
Temperature Dependent ◽  
Appearance Time ◽  
Portal Venous Blood ◽  
Kinetics Of

The kinetics of the transepithelial movement of heavy metals were studied in the perfused rat jejunum in situ. The peak appearance time (TET) of Zn, Ni, and Cd in portal venous blood was determined after their transient (10 s) introduction into the intestinal lumen. Observed TET values for these metals were positively correlated with their affinities for metallothionein and agreed with those predicted on the basis of a linear three-compartment model that does not allow for paracellular pathways. Further evidence was provided to support the hypothesis that Cd absorption consists first of Cd binding to negative membrane charges followed by a temperature-dependent internalization step.

BIOSYNTHESIS OF C19 STEROIDS FROM 4-14C-CHOLESTEROL AND 7-3H-PREGNENOLONE IN VIVO: CONSIDERATION OF NEW PATHWAYS

1962 ◽  
Vol 40 (2) ◽  
pp. 188-202 ◽  
Author(s):  
Shlomo Burstein ◽  
Ralph I. Dorfman
Keyword(s):  
Adrenal Adenoma ◽  
Mevalonic Acid ◽  
Compartment Model ◽  
Side Chain ◽  
Partition Chromatography ◽  
Steroid Nucleus ◽  
Single Intravenous Injection ◽  
Two Compartment Model ◽  
Specific Activities

ABSTRACT 3H and 14C specific activities of dehydroepiandrosterone, androsterone, 3α-hydroxy-5β-androstan-17-one and 3α-hydroxy-5α-androst-16-ene (without dilution) have been determined following a single intravenous injection of 4-14C-cholesterol and 7α-3H-pregnenolone to a virilized woman with an adrenal adenoma and massive dehydroepiandrosterone excretion. Assuming a one compartment model, or a two compartment model in which the injected radioactivity enters the compartment in which the precursor is secreted exclusively, a new pathway by which dehydroepiandrosterone is formed from cholesterol not through pregnenolone and possibly by cleavage of the side chain C-17 and C-20 is indicated. Analysis of the data by a model in which pregnenolone is secreted into two separate compartments in which progesterone and dehydroepiandrosterone are made, respectively, would explain the findings without necessitating the assumption of a new pathway. 3α-Hydroxy-5α-androst-16-ene was isolated from urine following incubation with β-glucuronidase and partition chromatography on celite suggesting that this steroid is a genuine natural product as surmised by Prelog & Ruzicka (1944) and Brooksbank & Haslewood (1950). 2-14C-Mevalonate was shown to give rise to C19 steroids which is the first in vivo demonstration that mevalonic acid is a precursor of the steroid nucleus in man.

Determination of digesta fill and passage rate from nonabsorbed particulate phase markers using the single dosing method

1989 ◽  
Vol 67 (2) ◽  
pp. 488-494 ◽  
Author(s):  
D. F. Holleman ◽  
R. G. White
Keyword(s):  
Compartment Model ◽  
Time Dependent ◽  
Passage Rate ◽  
Fecal Output ◽  
Two Compartment Model ◽  
Significant Difference ◽  
Single Marker ◽  
Dependent Model ◽  
Digesta Passage

A method is given for analyzing particulate digestive marker data in terms of digesta fill, fecal output, and digesta passage times. The method applies the Stewart – Hamilton Principle to data obtained from a single marker dosing followed by feces sampling; it assumes steady-state conditions for the digesta, but makes no assumptions concerning compartmentalization of digesta. Data analyses are presented for an experiment with sheep in which a particle phase marker, cerium-141 chloride, was used. The estimate of fecal output obtained was 1.8 ± 2.2% (mean percent difference ± SE) greater than the actual fecal output; the in vivo estimate of total digesta fill was 3.3 ± 3.4% less than measured digesta fill. For comparison, the present data were also analyzed using two established compartment modeling approaches, namely a time-independent and a time-dependent two-compartment model. The only significant difference between the estimated parameters as obtained from the Stewart – Hamilton method and the compartmental models was a significantly shorter transit time as estimated by the time-dependent model.

scholarly journals Kinetics and secretion of placental growth hormone around parturition

2006 ◽  
Vol 154 (3) ◽  
pp. 449-457 ◽  
Author(s):  
Jens Fuglsang ◽  
Puk Sandager ◽  
Niels Møller ◽  
Sanne Fisker ◽  
Hans Ørskov ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Vaginal Delivery ◽  
Half Life ◽  
Late Phase ◽  
Compartment Model ◽  
Maternal Blood ◽  
Maternal Circulation ◽  
Blood Samples ◽  
Two Compartment Model ◽  
Placental Growth Hormone

Objective: During pregnancy, placental growth hormone (PGH) is secreted into the maternal circulation, replacing pituitary GH. It is controversial whether PGH levels decline during vaginal birth. After placental expulsion, PGH is eliminated from the maternal blood. GH binding protein (GHBP) and body mass index (BMI) influence GH kinetics, but their impact on PGH kinetics is unknown. The present study was undertaken to define the kinetics of PGH during vaginal delivery and Caesarian section and to relate these kinetics to GHBP and BMI. Design: A short term, prospective cohort study. Methods: Twelve women had repeated blood samples drawn during vaginal delivery. From 26 women undergoing planned Caesarian delivery (CS) repeated blood samples were withdrawn before, during and after the CS, allowing PGH half-life determination. Results: During vaginal delivery, median PGH values did not change before expulsion of the placenta, although individual fluctuations were seen. Clearance of PGH from the maternal circulation was best described by a two-compartment model. The initial half-life of serum PGH was (mean ± s.d.) 5.8 ± 2.4 min, and the late half-life was (median) 87.0 min (range: 25.1–679.6 min). The late half-life was correlated to the pre-gestational BMI (r = 0.39, P = 0.047), but not to the serum GHBP concentration. Conclusions: Serum PGH did not decrease significantly during vaginal delivery. Elimination of PGH fitted a two-compartment model, with an estimated initial half-life of 5.8 min. The late phase serum half-life of PGH was related to BMI, suggesting a role for maternal fat mass in PGH metabolism.

Single Dose Administration of rFVIIa and NN1731 in Two Hemophilia A Dogs.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3144-3144 ◽  
Author(s):  
Mirella Ezban ◽  
Lone Frost ◽  
Dorthe Viuff ◽  
Judi Møss ◽  
Mark Kloos ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Ex Vivo ◽  
Compartment Model ◽  
Initial Distribution ◽  
Coagulation Assays ◽  
Two Compartment Model ◽  
Dose Study ◽  
Related Proteins

Abstract Introduction: The objective of this pilot study was to evaluate and compare the pharmacokinetic and pharmacodynamic (PK/PD) profile of rFVIIa and NN1731 in two hemophilia A dogs. In addition, it was the aim to evaluate the use of TEG for monitoring rFVIIa/NN1731 activity after in vivo administration and to compare with ex vivo spiking data from a previous study. NN1731 is a new rFVIIa analoge with enhanced activity (Allen et al. Arterioscler. Thromb. Vasc. Biol.2007;27:683–689). In hemophilia patients as well as hemophilia dogs the clot formation is impaired and reflected in coagulation assays such as thromboelastography (TEG) and APTT. The choice of hemophilia dogs is based upon the knowledge that the pharmacokinetics of human coagulations factors (FVIII, FIX and rFVIIa) as well as the effective dose is similar to that in humans. In normal dogs, it is not possible to evaluate the effect of these procoagulant proteins in coagulation assays as no impaired clotting is observed. Methods: rFVIIa and NN1731 (280 μg/kg IV) were administered to two hemophilia dogs on separate days and plasma samples collected at different time points. FVIIa activity was measured by the FVIIa clot assay and values were used for pharmacokinetic assessment. The same pharmacokinetic models, a non-compartmental method and a two compartment model, respectively, were used as was the case in the First Human Dosing (FHD) trial of NN1731 (NN1731–1639). Analysis of PD markers in dogs included: APTT, PT and whole blood thromboelastography analysis, recently developed for use in hemophilia dogs. Results: Based on the FVIIa activity profile in the two dogs it was observed that the values obtained at the first time point (C5 min), were higher after treatment with NN1731 than after rFVIIa. All activity based assays including TEG demonstrated that NN1731 was cleared faster than rFVIIa., FVIIa activity (FVIIa clot assay), showed a rapid initial distribution and/or elimination of FVIIa activity (t1/2α:0.3 h) followed by a less rapid elimination phase (t½β:3.5 h). Similar profile and values were obtained for NN1731 in the FHD dose study (J. Møss et al, ISTH, 2007) Conclusions: This study indicates that in hemophilia A dogs, NN1731 and rFVIIa have distinct PK profiles and very similar to what is observed in man. All activity assays show the same qualitative profile, the FVIIa clot assay being the most sensitive assay. The TEG data obtained in vivo are in accordance with the values obtained after in vitro spiking. The data support the use of hemophilia dogs for evaluating the pharmacokinetic and pharmacodynamic profiles of FVIIa related proteins.

Influence of nephrectomy on the glucoregulatory response to insulin administration in the rat

1980 ◽  
Vol 58 (3) ◽  
pp. 301-305 ◽  
Author(s):  
Gavino Perez ◽  
Giacomo Carteni ◽  
Biagio Ungaro ◽  
Luigi Saccà
Keyword(s):  
Plasma Concentrations ◽  
Insulin Injection ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Metabolic Clearance ◽  
The Face ◽  
Plasma Insulin Levels ◽  
Glucagon And Insulin ◽  
Glucose Output

Insulin sensitivity and resistance were examined in vivo in uremic rats by using tracer methods which permit the assessment of "non-steady-state" glucose kinetics. By relating the changes in the rates of glucose output by the liver (Ra), uptake by tissues (Rd), and metabolic clearance (MCR) to immunoreactive glucagon and insulin, it was possible to assess the tissue sensitivity to physiologic and supraphysiologic levels of these two hormones and the site of insulin resistance. The effect of an intravenous injection of insulin (100 mU) on glucose turnover was studied in acutely uremic rats 15 h after bilateral nephrectomy and in sham-operated controls, in the postabsorptive state. Glucose output by the liver and uptake by tissues were determined by the primed constant infusion technique using [3-3H]glucose. Under basal conditions, no significant differences in Ra and Rd between the two groups were observed, while a significant hyperglycemia and a reduced glucose metabolic clearance rate in the face of hyperglucagonemia and normal plasma insulin levels were observed in nephrectomized rats. After insulin injection, the glycemic curves were similar in the two groups, while Ra, Rd, and MCR displayed significantly lower values in nephrectomized rats in the face of higher plasma concentrations of insulin and glucagon. It was concluded that acute uremia in the rat is characterized by a loss of the normal ability of insulin to promote peripheral glucose uptake with retention of hepatic sensitivity to insulin.

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