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.

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.

Effects of inhibitors of cyclic nucleotide phosphodiesterase on actions of cholecystokinin, bombesin, and carbachol on pancreatic acini

1983 ◽  
Vol 245 (5) ◽  
pp. G676-G680
Author(s):  
J. D. Gardner ◽  
V. E. Sutliff ◽  
M. D. Walker ◽  
R. T. Jensen
Keyword(s):  
Dose Response ◽  
Cyclic Nucleotide ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Enzyme Secretion ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Rightward Shift ◽  
Stimulation Of

In dispersed acini from guinea pig pancreas two inhibitors of cyclic nucleotide phosphodiesterase, Ro 20-1724 and 3-isobutyl-1-methylxanthine (IBMX), augmented the increase in amylase secretion caused by supramaximal concentrations of cholecystokinin but did not alter the stimulation of enzyme secretion caused by bombesin. The augmentations of the action of cholecystokinin caused by Ro 20-1724 or IBMX could be reproduced by 8-bromo-cAMP. When tested alone or with theophylline, cholecystokinin did not alter cAMP in pancreatic acini; however, with Ro 20-1724 or IBMX, concentrations of cholecystokinin that were supramaximal for stimulating amylase secretion caused a significant increase in cellular cAMP. These findings indicate that Ro 20-1724 and IBMX augment the action of cholecystokinin on enzyme secretion by inhibiting cyclic nucleotide phosphodiesterase and allowing a significant cholecystokinin-induced increase in cellular cAMP. IBMX but not Ro 20-1724 caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion caused by carbachol. IBMX also caused a parallel rightward shift in the dose-response curve for the stimulation of outflux of 45Ca caused by carbachol. These results indicate that IBMX, but not Ro 20-1724, can function as a muscarinic cholinergic antagonist.

VIP stimulation of β-naphthylamidase activity in guinea-pig thyroid sections

1985 ◽  
Vol 109 (4) ◽  
pp. 505-510 ◽  
Author(s):  
P. A. Ealey ◽  
N.J. Marshall ◽  
R. P. Ekins
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Receptor Site ◽  
Dose Response Curve ◽  
Tsh Receptor ◽  
Maximal Response ◽  
Cytochemical Bioassay ◽  
Order Of Magnitude ◽  
Specific Receptors ◽  
Stimulation Of

Abstract. Subsequent to the discovery of vasoactive intestinal peptide (VIP) in the thyroid gland, VIP has been shown to stimulate various thyroid functions. The site of interaction of VIP with the thyroid follicular cell is at present not known, and this study has used the ultrasensitive cytochemical bioassay (CBA) for thyroid stimulators to investigate this further. Exposure of thyroid sections for 3 min to VIP resulted in increased naphthylamidase activity, with half-maximal response observed at 3 × 10−13 m VIP. This response to such low doses of VIP is consistent with the CBA being ultrasensitive to other thyroid stimulators e.g. TSH, thyroid stimulating antibodies and forskolin. The response to VIP was abolished by rabbit anti-VIP antiserum. The dose-response curve to VIP was bell-shaped (as with the other stimulators), maximal stimulation occurring at 10−12 m VIP. In contrast, however, to other thyroid stimulators, namely TSH, LATS-B and 3 monoclonal stimulating antibodies, whose ascending limbs of the doseresponse curves extended over 3-4 orders of magnitude, the VIP curve rose rapidly from basal to maximal tissue stimulation from 10−13 to 10−12m VIP, i.e. one order of magnitude. This unusual dose-response curve to VIP was parallel to that produced by forskolin. 11E8, a monoclonal 'blocking' antibody which is a potent inhibitor of TSH stimulation, did not 'block' forskolin stimulation, consistent with the belief that forskolin acts at a post-receptor site. However, unlike forskolin, VIP was inhibited by monoclonal 11E8, which may imply a hitherto unexpected involvement of the TSH receptor in VIP stimulation of the thyroid or, alternatively, steric inhibition by 11E8 when bound to the TSH receptor of VIP interaction with adjacent VIP-specific receptors.

Forskolin stimulation of naphthylamidase in guinea pig thyroid sections detected with a cytochemical bioassay

1985 ◽  
Vol 108 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Patricia A. Ealey ◽  
Leonard D. Kohn ◽  
Nicholas J. Marshall ◽  
Roger P. Ekins
Keyword(s):  
Guinea Pig ◽  
Dose Response ◽  
Response Curve ◽  
Thyroid Tissue ◽  
Receptor Site ◽  
Dose Response Curve ◽  
Cytochemical Bioassay ◽  
Surface Receptor ◽  
Stimulation Of ◽  
Endocrine Tissues

Abstract. Forskolin, from the roots of the Indian medicinal plant Coleus forskohlii, has recently been shown to be a potent stimulator of adenylate cyclase in many systems, including endocrine tissues such as the thyroid gland. We describe forskolin activation of β-naphthylamidase activity in guinea pig thyroid tissue using the cytochemical bioassay (CBA) for thyroid stimulators. This CBA is the most sensitive bioassay for TSH and LATS-B currently available, being able to detect stimulation by doses as low as 10−5 mU TSH/l and 10−9 mU LATS-B/l. The dose-response curve to forskolin was bell-shaped (as is seen with TSH and LATS-B) with the ascending limb of the curve produced by 10−13 m to 10−12 m forskolin after a 3 min exposure time. Maximal stimulation was observed with 10−12m forskolin. However, the dose-response curve to forskolin was not parallel to that given by TSH, the slope of the ascending limb being much greater. It has been suggested that stimulation of β-naphthylamidase activity in the CBA is via cAMP. We report that dibutyryl cAMP at doses from 10−16m to 10−11 m produces a bell-shaped dose-response curve with a very broad peak response, again not parallel to that produced by TSH. Forskolin activation of β-naphthylamidase in the CBA is unaffected by a 1:106 dilution of 11E8, a monoclonal antibody raised against solubilised TSH receptors, which binds to the TSH receptor and inhibits TSH stimulation. Although the precise location of forskolin action is not known, this is further evidence that forskolin acts at a post-surface receptor site.

Role of Endothelial K + Channels in NO-Dependent Vasorelaxant Responses to Acetylcholine in Rat Aorta.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 698-698
Author(s):  
John Quilley ◽  
Yue Qiu
Keyword(s):  
Dose Response ◽  
Response Curve ◽  
Rat Aorta ◽  
Dose Response Curve ◽  
Response Curves ◽  
K Channels ◽  
Voltage Dependent ◽  
The Right ◽  
Stimulation Of

P30 Endothelium-dependent vasorelaxant responses to acetylcholine (Ach) in rat aorta are mediated solely by NO. Rings precontracted with U46619 were used to investigate the role of endothelial K + channels. Thus, any effect of K + channel inhibitors on Ach responses in the absence of an effect on those to nitroprusside (NP) can be attributed to interference with Ach-induced stimulation of NO. Vasorelaxant responses to Ach (log EC 50 -7.29M) were abolished by removal of the endothelium or inhibition of NO synthesis with nitroarginine (100μM) which potentiated responses to NP (log EC 50 -9.41M vs -8.47M for control). In the presence of TEA (10mM) to inhibit K + channels, the dose-response curve for Ach, but not NP, was shifted to the right (log EC 50 -6.06). Elevation of extracellular K + (25mM KCl)also shifted the dose-response curve for Ach to the right. Inhibitors of specific types of K + channels: BaCl 2 (30μM), apamin (100nM), glibenclamide (10μM), charybdotoxin (50nM) and iberiotoxin (100nM) were without effect on dose-response curves to either Ach or NP. However, the combination of apamin (100nM) and charybdotoxin (50nM) but not apamin plus iberiotoxin, reduced relaxant responses to Ach (log EC 50 -6.95M) without affecting those to NP.These results confirm that Ach-induced relaxation of rat aorta is mediated entirely by endothelium-derived NO, the release of which apparently involves hyperpolarization of the endothelium. This effect is dependent on activation of a K + channel that is blocked by a combination of apamin/charybdotoxin but neither agent alone, possibly indicating characteristics of both Ca 2+ - activated and voltage-dependent K + channels.

2-Chloroadenosine increases calcium mobilization from mouse calvaria in vitro

1982 ◽  
Vol 100 (2) ◽  
pp. 313-320 ◽  
Author(s):  
Ulf Lerner ◽  
Bertil B. Fredholm
Keyword(s):  
Bone Resorption ◽  
Cyclic Amp ◽  
Bone Tissue ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Cyclic Amp Accumulation ◽  
Adenosine Analogue ◽  
Stimulation Of

Abstract. The effect of 2-chloroadenosine on bone resorption and on cyclic AMP formation in murine calvarial bones in vitro was investigated. 2-Chloroadenosine increased the release of 45Ca from the cultured bones, but had no effect on dead bones, indicating that the effect is cell mediated. The adenosine analogue remained in the medium for 48 h and caused a transient stimulation of the formation of cyclic AMP. The dose-response curve for the stimulatory effect on cyclic AMP accumulation was linear up to 10−4m. The dose-response curve for 45Ca release was linear from 3 × 10−7 m to 3 × 10−5 m but then showed a decline in the response. 8-Bromo cyclic AMP inhibited the release of 45Ca in 24 h cultures. The initial stimulatory effect on bone resorption by 2-chloroadenosine may therefore not depend on cyclic AMP. The level of inosine increased during culture indicating that adenosine is formed by bone 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.

Lipolysis in Adipose Tissue: Model-Fitting to a Noradrenaline Dose-Response Curve

1974 ◽  
Vol 2 (3) ◽  
pp. 393-395 ◽  
Author(s):  
DERMOT M. F. COOPER ◽  
MARIE-LOUISE RABOUHANS ◽  
J. ISLWYN DAVIES ◽  
DAVID EVERETT
Keyword(s):  
Adipose Tissue ◽  
Dose Response ◽  
Response Curve ◽  
Model Fitting ◽  
Dose Response Curve ◽  
Tissue Model

Secretagogue stimulation of [14C]aminopyrine accumulation by isolated canine parietal cells

1980 ◽  
Vol 238 (4) ◽  
pp. G366-G375 ◽  
Author(s):  
A. H. Soll
Keyword(s):  
Parietal Cell ◽  
Dose Response ◽  
Response Curve ◽  
Dissociation Constants ◽  
Receptor Site ◽  
Dose Response Curve ◽  
Cell Content ◽  
Parallel Displacement ◽  
Mucosal Cells ◽  
Stimulation Of

Isolated canine gastric mucosal cells accumulate [14C]aminopyrine (AP) when treated with histamine, gastrin, and carbachol. In fractions of varying parietal cell content, this accumulation of AP correlated with the parietal cell content. Cimetidine caused parallel displacement of the dose-response curve to histamine, but failed to alter the response to carbachol or gastrin. Atropine caused parallel displacement of the dose-response curve to carbachol, but failed to inhibit the response to histamine or gastrin. The dissociation constants (Kb) for cimetidine inhibition of histamine and for atropine inhibition of carbachol were found to be 1.0 micro M and 1.3 nM, respectively, values comparable to those reported for other tissues. Thus, the isolated parietal cell appears to have pharmacologically typical H2- and muscarinic receptors, with gastrin acting at a third receptor site. Isobutyl methylxanthine (IMX) and the cAMP analogues dibutyryl cAMP (DBcAMP) and 8-bromo cAMP (but not the same analogues of cGMP) also stimulated AP accumulation. Atropine failed to inhibit the responses to IMX or DBcAMP, whereas cimetidine did inhibit the response to IMX, but not to DBcAMP.

Effects of inhibitors of cyclic nucleotide phosphodiesterase on the actions of vasoactive intestinal peptide and secretin on pancreatic acini

1982 ◽  
Vol 242 (6) ◽  
pp. G547-G551
Author(s):  
J. D. Gardner ◽  
L. Y. Korman ◽  
M. D. Walker ◽  
V. E. Sutliff
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Dose Response ◽  
Cyclic Nucleotide ◽  
Response Curve ◽  
Phosphodiesterase Inhibitor ◽  
Dose Response Curve ◽  
Cyclic Nucleotide Phosphodiesterase ◽  
Amylase Secretion ◽  
Pancreatic Acini ◽  
Stimulation Of

Theophylline, 3-isobutyl-1-methylxanthine (IBMX), and Ro 20-1724 each augmented the increase in cAMP and the stimulation of amylase secretion caused by vasoactive intestinal peptide (VIP) or secretin. With IBMX the dose-response curve for the stimulation of amylase secretion caused by VIP or secretin spanned a range of lower concentrations than did that obtained with Ro 20-1724, which in turn spanned a range of lower concentrations than did that obtained with theophylline. The configuration of the dose-response curve for the action of VIP on cAMP differed with each phosphodiesterase inhibitor tested. With Ro 20-1724 the dose-response curve was monophasic, whereas with the two methylxanthines the dose-response curve was biphasic. With theophylline the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. The configuration of the dose-response curve for the action of secretin on cAMP also differed with each phosphodiesterase inhibitor tested. With theophylline the dose-response curve was monophasic, whereas with Ro 20-1724 and IBMX the dose-response curve was biphasic. With Ro-20-1724 the magnitude of the second component of the dose-response curve was larger than the first; with IBMX the magnitude of the first component was larger than the second. These results indicate that cAMP is compartmentalized in pancreatic acinar cells and that the different compartments of cAMP are affected differently by various inhibitors of cyclic nucleotide phosphodiesterase. These findings also suggest that the different compartments of cAMP are acted on by phosphodiesterases with different sensitivities to various inhibitors.

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