scholarly journals Effects of insulin on lipolysis and lipogenesis in adipocytes from genetically obese (ob/ob) mice

1979 ◽  
Vol 184 (1) ◽  
pp. 107-112 ◽  
Author(s):  
J A Carnie ◽  
D G Smith ◽  
M Mavris-Vavayannis
Keyword(s):  
Adipose Tissue ◽  
Dose Response ◽  
Response Curve ◽  
Insulin Dose ◽  
Insulin Response ◽  
Hormonal Control ◽  
Dose Response Curve ◽  
Obese Mice ◽  
The Right

A method for the preparation of isolated adipocytes from obese mice is described. Similar yields of adipocytes (50–60%), as judged by several criteria, are obtained from obese mice and lean controls. Few fat-globules and no free nuclei were observed in cell preparations, which are metabolically active, respond to hormonal control and appear to be representative of intact adipose tissue. Noradrenaline-stimulated lipolysis was inhibited by insulin, equally in adipocytes from lean and obese mice. Inhibition in obese cells required exogenous glucose, and the insulin dose–response curve was shifted to the right. Basal lipogenesis from glucose was higher in adipocytes from obese mice, and the stimulatory effect of insulin was greater in cells from obese mice compared with lean controls. A rightward shift in the insulin dose–response curve was again observed with cells from obese animals. This suggests that adipose tissue from obese mice is insulin-sensitive at the high blood insulin concentrations found in vivo. The resistance of obese mice to the hypoglycaemic effect of exogenous insulin and their impaired tolerance to glucose loading appear to be associated with an impaired insulin response by muscle rather than by adipose tissue.

POTENTIATION OF INSULIN RELEASE BY GLUCOSE IN MAN

1975 ◽  
Vol 79 (3) ◽  
pp. 483-501 ◽  
Author(s):  
Erol Cerasi
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Insulin Dose ◽  
Late Phase ◽  
Insulin Response ◽  
Glucose Infusion ◽  
Dose Response Curve ◽  
Maximum Effect ◽  
Releasing Effect ◽  
Effect Of Glucose

ABSTRACT The effect of repeating a 60 min glucose infusion at a 40 to 70 min interval was investigated after an overnight fast in 14 healthy, non-obese subjects with normal glucose tolerance and normal insulin response to glucose administration. When a hyperglycaemic plateau of around 300 mg/100 ml was induced by the first glucose infusion, the insulin response to a second challenge was enhanced over the range of stimulations used. Both the early and late phase insulin responses were amplified, the enhancement being more marked with higher stimulatory levels of glucose. The blood glucose-insulin dose-response curve became steeper after pretreatment with glucose, the stimulatory threshold level not being altered. These findings suggest that the synergism between the glucose pretreatment, and the insulin releasing effect of glucose, is of multiplicative type, resulting in increase of the maximum effect of the glucose. The dose-dependency of this potentiation was investigated by keeping the second glucose challenge at a constant level and altering the dose of the first infusion. It was necessary to reach hyperglycaemias around and above 300 mg/100 ml during the first infusion in order to obtain enhancement of the insulin response to the second stimulus. The dose-response curve of the potentiating effect of glucose is thus displayed towards the right when compared with that describing the insulin releasing effect of glucose, which has its threshold around 100 mg/100 ml. It is suggested that glucose exerts a dual effect on the pancreatic islets: an immediate one which initiates the release of insulin, and a time-bound one which modulates the first action.

scholarly journals Insulin, dexamethasone and their interactions in the control of glucose metabolism in adipose tissue from lactating and nonlactating sheep

1988 ◽  
Vol 256 (2) ◽  
pp. 509-514 ◽  
Author(s):  
R G Vernon ◽  
E Taylor
Keyword(s):  
Adipose Tissue ◽  
Glucose Uptake ◽  
Dose Response ◽  
Response Curve ◽  
Insulin Dose ◽  
Dose Response Curve ◽  
Acetate Uptake ◽  
Lactate Output ◽  
Acetate Utilization ◽  
Stimulation Of

1. Lactation results in decreased glucose and acetate utilization and increased lactate output by sheep adipose tissue. 2. The ability of insulin to stimulate acetate uptake was lost in adipose tissue from lactating sheep, whereas both the response and the sensitivity (ED50) for insulin for stimulation of glucose conversion into products other than lactate were decreased. These impairments were partly restored by prolonged incubation of adipose tissue for 48 h. 3. The ability of insulin to stimulate lactate output was not altered by lactation. 4. Dexamethasone inhibited glucose uptake, lactate output and glycerol output in adipose tissue from both non-lactating and lactating sheep, with an ED50 of about 1 nM. Dexamethasone inhibited acetate uptake by adipose tissue from non-lactating sheep, but this effect was not observed with adipose tissue from lactating sheep. 5. Dexamethasone inhibited the stimulation of glucose uptake at all concentrations of insulin used; the effect varied with insulin concentration and resulted in an accentuation of the insulin dose-response curve. The insulin dose-response curve in the presence of dexamethasone was muted during lactation. 6. The overall effect of these adaptations is to ensure that glucose and acetate utilization by adipose tissue after an insulin surge is diminished during lactation.

Validation of a practical in vivo insulin dose-response curve in man

Metabolism ◽  
1982 ◽  
Vol 31 (4) ◽  
pp. 354-361 ◽  
Author(s):  
J. Proietto ◽  
M. Harewood ◽  
P. Aitken ◽  
A. Nankervis ◽  
G. Caruso ◽  
...  
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Insulin Dose ◽  
Dose Response Curve

Study of dosimetric characteristics of a commercial optically stimulated luminescence system

2017 ◽  
Vol 16 (4) ◽  
pp. 461-475 ◽  
Author(s):  
Gourav K. Jain ◽  
Arun Chougule ◽  
Ananth Kaliyamoorthy ◽  
Suresh K. Akula
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Light Exposure ◽  
Dose Range ◽  
Optically Stimulated Luminescence ◽  
Dose Response Curve ◽  
Field Size ◽  
In Vivo Dosimetry ◽  
Detector Response

AbstractBackgroundOptically stimulated luminescence dosimeters (OSLDs) have a number of advantages in radiation dosimetry making them an excellent dosimeter for in vivo dosimetry. The study aimed to study the dosimetric characteristics of a commercial optically stimulated luminescence (OSL) system by Landauer Inc., before using it for routine clinical practice for in vivo dosimetry in radiotherapy. Further, this study also aimed to investigate the cause of variability found in the literature in a few dosimetric parameters of carbon-doped aluminium oxide (Al2O3:C).Materials and methodsThe commercial OSLD system uses Al2O3:C nanoDotTM as an active radiation detector and InLightTM microStar® as a readout assembly. Inter-detector response, energy, dose rate, field size and depth dependency of the detector response were evaluated for all available clinical range of photon beam energies in radiotherapy.ResultsInter-detector variation in OSLD response was found within 3·44%. After single light exposure for the OSL readout, detector reading decreased by 0·29% per reading. The dose linearity was investigated between dose range 50–400 cGy. The dose response curve was found to be linear until 250 cGy, after this dose, the dose response curve was found to be supra-linear in nature. OSLD response was found to be energy independent for Co60 to 10 MV photon energies.ConclusionsThe cause of variability found in the literature for some dosimetric characteristics of Al2O3:C is due to the difference in general geometry, construction of dosimeter, geometric condition of irradiation, phantom material and geometry, beam energy. In addition, the irradiation history of detector used and difference in readout methodologies had varying degree of uncertainties in measurements. However, the large surface area of the detector placed in the phantom with sufficient build-up and backscatter irradiated perpendicularly to incident radiation in Co60 beam is a good method of choice for the calibration of a dosimeter. Understanding the OSLD response with all dosimetric parameters may help us in estimation of accurate dose delivered to patient during radiotherapy treatment.

Copper inhibits pressor responses to noradrenaline but not potassium. Interactions with prostaglandins E1, E2, and I2 and penicillamine

1979 ◽  
Vol 57 (1) ◽  
pp. 35-40 ◽  
Author(s):  
S. C. Cunnane ◽  
H. Zinner ◽  
D. F. Horrobin ◽  
M. S. Manku ◽  
R. O. Morgan ◽  
...  
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Biological Action ◽  
Dose Response Curve ◽  
Low Concentrations ◽  
Pressor Responses ◽  
The Right ◽  
Copper Effect

Low concentrations of copper inhibited responses to norepinephrine and angiotensin (IC50 3 × 10−6 M) but not to potassium in rat mesenteric vascular preparations perfused either with buffer or indomethacin and prostaglandin (PGE2). The dose–response curve was not shifted by indomethacin, imidazole, or PGE2 but was moved to the right by 2.8 × 10−11 M PGE1 and to the left by 2.8 × 10−7 M PGE1. These effects of copper are similar to the effects of PGI2 in the preparation. Copper moved the PGI2 dose–response curve against noradrenaline in parallel to the left, suggesting that the two were interacting at some point. Penicillamine, which may stimulate PGE1 synthesis, had PGE1-like interactions with the copper effect, suggesting that its value in Wilson's disease may be partly due to antagonism of the biological action of copper as well as to its copper-chelating properties.

Alteration of islet neurotransmitter sensitivity following ventromedial hypothalamic lesion

1983 ◽  
Vol 244 (5) ◽  
pp. R635-R640 ◽  
Author(s):  
L. A. Campfield ◽  
F. J. Smith
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Dose Response ◽  
Response Curve ◽  
Pancreatic Beta Cell ◽  
Dose Response Curve ◽  
Norepinephrine Dose ◽  
Increased Sensitivity ◽  
The Right ◽  
Glucose Responsiveness

Recent studies suggest that alterations in autonomic neural activity may mediate the obese state observed following ventromedial hypothalamic (VMH) lesion. To assess the role of these alterations in the increased glucose responsiveness of the beta-cell observed in this state, we have determined the sensitivity of insulin secretion to norepinephrine or/and acetylcholine in statically incubated pancreatic islets from rats 30-40 days after VMH lesion. In islets from VMH-lesioned rats compared with islets from sham-operated and intact rats, the acetylcholine dose-response curve was shifted down and to the right, indicating a decreased sensitivity, whereas the norepinephrine dose-response curve was translated to the left, indicating an increased sensitivity. The interaction profile, which summarizes combined neurotransmitter exposure on insulin secretion, was shifted in the direction of net inhibition. Thus it was concluded that, following VMH lesion, autonomic neurotransmitter sensitivity of the pancreatic beta-cell was altered. It is suggested that these alterations play a role in the adaptation of the beta-cell to the experimentally induced obese state.

scholarly journals Cd2 Sets Quantitative Thresholds in T Cell Activation

1999 ◽  
Vol 190 (10) ◽  
pp. 1383-1392 ◽  
Author(s):  
Martin F. Bachmann ◽  
Marijke Barner ◽  
Manfred Kopf
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Dose Response ◽  
Response Curve ◽  
Cell Activation ◽  
Dose Response Curve ◽  
Lymphocyte Function

It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell–antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose–response curve in vitro by a factor of 3–10. In comparison, stimulation of T cells in the absence of lymphocyte function–associated antigen (LFA)-1–intercellular adhesion molecule (ICAM)-1 interaction shifted the dose–response curve by a factor of 10, whereas absence of both CD2–CD48 and LFA-1–ICAM-1 interactions shifted the response by a factor of ∼100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca2+ fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

Leukotriene receptor on U-937 cells: discriminatory responses to leukotrienes C4 and D4

1991 ◽  
Vol 261 (2) ◽  
pp. L164-L171 ◽  
Author(s):  
L. A. Wetmore ◽  
N. P. Gerard ◽  
D. K. Herron ◽  
N. G. Bollinger ◽  
S. R. Baker ◽  
...  
Keyword(s):  
Cell Surface ◽  
Dose Response ◽  
Response Curve ◽  
Spatial Configuration ◽  
Dose Response Curve ◽  
Striking Difference ◽  
Cell Surface Receptors ◽  
Leukotriene D4 ◽  
Surface Receptors ◽  
The Right

Dimethyl sulfoxide (DMSO)-differentiated U-937 cells develop cell surface receptors for leukotrienes that, when stimulated, initiate a transient increase in intracellular calcium concentration [( Ca2+]i). We investigated the calcium transient that occurs after addition of leukotriene C4 (LTC4) to determine whether it occurs due to 1) the bioconversion of LTC4 to leukotriene D4 (LTD4), which then acts at the LTD4 receptor; 2) the direct action of LTC4 at the LTD4 receptor; or 3) the action of LTC4 at a receptor selective for LTC4. Bioconversion of [3H]LTC4 to [3H]LTD4 was inhibited by 98% when DMSO-differentiated U-937 cells were incubated with 10 mM AT-125 compared with control cells. The dose-response curve for LTC4, with [Ca2+]i as the index of response, was parallel to that for LTD4 but was significantly (P less than 0.0001) shifted 1.6 +/- 0.11 log units to the right. AT-125 did not change the response to LTD4 but the LTC4 dose-response curve was shifted on additional 1.7 logo units to the right. The antagonists SKF 104353 (1 microM) and LY 171883 (10 microM) shifted the dose-response curve for LTD4 3.0 +/- 0.23 and 2.5 +/- 0.23 log units, respectively, to the right and completely inhibited the change in [Ca2+]i due to LTC4 in the presence of 10 mM AT-125. Molecular modeling studies demonstrated a striking difference in the spatial configuration of LTC4 and LTD4, likely accounting for the ability of cell surface receptors to discriminate between the effects of these two molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Histamine Receptors in Normal Human Bronchi

1980 ◽  
Vol 58 (6) ◽  
pp. 537-544 ◽  
Author(s):  
Noemi M. Eiser ◽  
Jane Mills ◽  
K. D. McRae ◽  
P. D. Snashall ◽  
A. Guz
Keyword(s):  
Receptor Antagonist ◽  
Dose Response ◽  
Response Curve ◽  
Normal Subjects ◽  
Dose Response Curve ◽  
Significant Shift ◽  
H2 Receptor Antagonist ◽  
Anticholinergic Activity ◽  
H2 Receptor ◽  
The Right

1. Nine normal subjects inhaled increasing concentrations of histamine aerosol from an aerosol generator attached to a breath-actuated dosimeter. The responses were monitored by measuring specific airways-conductance in a body plethysmograph, and the results were expressed as cumulative log dose-response curves. On separate days, histamine challenges were repeated after intravenous injections of sodium chloride solution (placebo), or an H1-receptor antagonist chlorpheniramine, or an H2-receptor antagonist cimetidine, or H1- and H2-receptor antagonists together. The anticholinergic activity of chlorpheniramine was estimated by comparing the effect of chlorpheniramine and atropine on methacholine challenge. 2. In all subjects the response to histamine was reproducible. Analysis of the variance showed that placebo did not alter the histamine dose-response curve significantly. In contrast, chlorpheniramine produced a large shift in the histamine dose-response curve to the right and cimetidine produced a significant shift of this curve to the right only at the highest dose of histamine. A combination of cimetidine and chlorpheniramine produced a shift not significantly different from that seen with chlorpheniramine alone. Chlorpheniramine showed no significant anticholinergic activity in this study. 3. In the normal subjects histamine-induced bronchoconstriction appeared to be mediated predominantly by the H1-receptors. The H2-receptor contributed very little to this bronchoconstriction.

Postsynaptic potentiation and desensitization in frog neuromuscular junction

1988 ◽  
Vol 66 (5) ◽  
pp. 624-629 ◽  
Author(s):  
M. I. Glavinqvić
Keyword(s):  
Neuromuscular Junction ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Maximal Response ◽  
Frog Neuromuscular Junction ◽  
Receptor Complexes ◽  
Fractional Increase ◽  
The Right ◽  
Postsynaptic Potentiation

The fractional increase in ACh responses that occurs at the beginning of each train of iontophoretically applied ACh pulses has been examined at the frog neuromuscular junction at room temperature, in the presence of active cholinesterase, during desensitization produced by a rapid sequence (every 20 s) of short (5 Hz, 5 s) iontophoretic trains of ACh. The fractional increase in ACh responses, which is used as an indicator of postsynaptic potentiation, becomes progressively greater with ACh application, often markedly (>100%), although ACh responses are greatly reduced (as much as 90%) owing to desensitization. Clearly postsynaptic potentiation can exist concomitantly with desensitization. In addition, the dose–response curve is shifted to the right and its maximal response is diminished. The shift in the dose–response curve to the right, which can explain greater postsynaptic potentiation, is unlikely to be caused by accumulation of "monoligand-bound ACh receptor complexes," since experiments were done with active cholinesterase. The shift probably results from a greater number of desensitized receptors which, because of their large affinity for ACh molecules, serve as "high affinity traps." A small decrease of the maximal dose–response suggests only a small fractional decrease in the number of activable receptors, whereas a large shift to the right indicates a large fractional increase in the number of desensitized receptors. It appears that prior to ACh application only a small fraction of all receptors are desensitized. Alternatively, the shift to the right occurs because the cooperative action of ACh on receptors increases during desensitization.

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