scholarly journals Distinctive effects of glucagon on gluconeogenesis and ketogenesis in hepatocytes isolated from normal and biotin-deficient rats

1978 ◽  
Vol 172 (3) ◽  
pp. 517-521 ◽  
Author(s):  
E A Siess ◽  
D G Brocks ◽  
O H Wieland

In hepatocytes from 48 h-starved rats identical glucagon dose-response curves were obtained for the stimulation of gluconeogenesis from lactate, for ketogenesis and for the decreasing of the C5-dicarboxylate pool. Glucagon (20 nM) caused a 5-fold increase in 3-hydroxybutyrate formation, but decreased acetoacetate production 50% of that of the control. In hepatocytes from biotin-deficient rats glucagon no longer stimulated gluconeogenesis from lactate, but still produced its effects on the mitochondrial redox state and the C5-dicarboxylate pool. The results suggest that the primary site of the hormone action on gluconeogenesis is located within the mitochondria rather than in the cytosol.

1956 ◽  
Vol 34 (1) ◽  
pp. 713-720 ◽  
Author(s):  
R. J. Young ◽  
C. C. Lucas ◽  
Jean M. Patterson ◽  
C. H. Best

Dose–response curves have been obtained showing the effects, in weanling rats, of graded doses of choline, betaine, and methionine, respectively, when added to a hypolipotropic diet. A comparison of the lipotropic activity made on the steep portions of the dose–response curves showed that at all liver fat values from normal to 27%, the ratio of betaine to choline necessary to produce a given level of fat was 3: 1. Essentially similar ratios were observed in the prevention of hemorrhagic kidney lesions and in the stimulation of growth. Methionine, at the lower doses, was as effective as betaine, on a molar basis, in maintaining a given level of liver fat. However, the higher levels of methionine were not as efficient. Methionine at the highest dosage used did not bring the liver fat entirely within the normal range.


1956 ◽  
Vol 34 (4) ◽  
pp. 713-720 ◽  
Author(s):  
R. J. Young ◽  
C. C. Lucas ◽  
Jean M. Patterson ◽  
C. H. Best

Dose–response curves have been obtained showing the effects, in weanling rats, of graded doses of choline, betaine, and methionine, respectively, when added to a hypolipotropic diet. A comparison of the lipotropic activity made on the steep portions of the dose–response curves showed that at all liver fat values from normal to 27%, the ratio of betaine to choline necessary to produce a given level of fat was 3: 1. Essentially similar ratios were observed in the prevention of hemorrhagic kidney lesions and in the stimulation of growth. Methionine, at the lower doses, was as effective as betaine, on a molar basis, in maintaining a given level of liver fat. However, the higher levels of methionine were not as efficient. Methionine at the highest dosage used did not bring the liver fat entirely within the normal range.


1986 ◽  
Vol 251 (4) ◽  
pp. G529-G537 ◽  
Author(s):  
M. C. Ruiz ◽  
F. Michelangeli

Gastrin tetrapeptide (TG) stimulation of H+ secretion and histamine release and their relationship were characterized in isolated amphibian gastric mucosa. TG released histamine and stimulated H+ secretion. Dose-response curves to TG showed nonparallel increases in both parameters. In tachyphylaxis experiments, there was no correlation between histamine release and H+ secretion. Comparison of cimetidine inhibitory dose-response curves of maximal TG or histamine stimulation showed a much higher sensitivity for TG-stimulated H+ secretion. This suggests that the pericellular histamine concentration released by TG was lower than that needed for maximal response. In mucosae maximally stimulated by histamine, TG induced a further increase in H+ secretion. In the presence of cimetidine, there was potentiation between TG and dibutyryl cAMP that was dependent on the presence of extracellular calcium. The results are interpreted to indicate that TG (or gastrin) stimulates H+ secretion through different mechanisms: 1) direct stimulation of the oxyntic cell dependent on extracellular calcium, 2) potentiation between gastrin and histamine, and 3) release of histamine from paracrine cells. Direct stimulation of the oxyntic cell by TG is not sufficient to trigger H+ secretion. Potentiation between TG and histamine at the oxyntic cell may result from interaction between TG-induced increases in intracellular Ca2+ and histamine-induced increases in intracellular cAMP.


Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5617-5625 ◽  
Author(s):  
Elisa K. Tyson ◽  
Roger Smith ◽  
Mark Read

Abstract As human pregnancy advances, CRH increases exponentially and is hypothesized to trigger the transition from myometrial quiescence to active contractions at labor. Paradoxically, CRH stimulates cAMP production, suggesting it should cause relaxation. To evaluate CRH as a mediator of quiescence, the effect of CRH on contractions in preterm and term myometria with concurrent progesterone (P4) was determined. In late gestation, we hypothesized that high concentrations of CRH down-regulate agonist-activated-cAMP relaxatory pathways and that increased phosphodiesterase (PDE) activity induces heterologous down-regulation of agonist-activated-cAMP pathways. CRH caused dose-dependent relaxation of spontaneously contracting myometrial strips of 31 ± 8% (mean ± sem; n = 12) and 35 ± 20% (n = 3) in term and preterm samples, respectively. CRH with P4 pretreatment caused a 40 ± 13% (n = 4) reduction in contractility, whereas in matched samples, CRH alone exerted a 26 ± 6% (n = 4) reduction, with a shift of CRH dose-response curves (P < 0.01, ANOVA). Pretreatment of strips with 10−7m CRH did not attenuate relaxation induced by subsequent CRH (n = 3) or salbutamol (β2-agonist) treatment (n = 9). PDE inhibition by rolipram showed a 2.2- and 1.5-fold increase in maximal relaxation induced by CRH and salbutamol, respectively, with a shift of both dose-response curves (P < 0.05 and P < 0.01, ANOVA). In conclusion, CRH at physiological concentrations acts synergistically with P4 contributing to myometrial quiescence. P4 withdrawal may reduce CRH-mediated relaxation. Our functional model does not support homologous or heterologous down-regulation of agonist-stimulated-cAMP pathways by high CRH concentrations. PDE inhibition potentiates CRH and salbutamol-induced relaxation. Up-regulation of PDEs, through chronic cAMP elevation by CRH, could provide a mechanism for down-regulation of agonist-stimulated-cAMP pathways at term.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.


1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.


2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  

2001 ◽  
Author(s):  
Quinton J. Nottingham ◽  
Jeffrey B. Birch ◽  
Barry A. Bodt

2021 ◽  
Vol 3 (1) ◽  
pp. 181-188
Author(s):  
Peter Bracke ◽  
Eowyn Van de Putte ◽  
Wouter R. Ryckaert

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.


2021 ◽  
Vol 21 (1) ◽  
pp. 69-110 ◽  
Author(s):  
Brian G. Vegetabile ◽  
Beth Ann Griffin ◽  
Donna L. Coffman ◽  
Matthew Cefalu ◽  
Michael W. Robbins ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document