scholarly journals Effects of the β-adrenoceptor agonist isoprenaline on insulin-sensitivity in soleus muscle of the rat

1986 ◽  
Vol 233 (2) ◽  
pp. 377-381 ◽  
Author(s):  
R A J Challiss ◽  
F J Lozeman ◽  
B Leighton ◽  
E A Newsholme
Keyword(s):  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Elevated Concentration ◽  
Hexose Transport ◽  
Muscle Preparation ◽  
Hexokinase Activity ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Glucose Phosphorylation ◽  
Stimulation Of

The interactions between a beta-adrenoceptor agonist (isoprenaline) and insulin on rates of hexose transport, glucose phosphorylation, glycogen synthesis and glycogenolysis were investigated in the incubated stripped soleus-muscle preparation of the rat. In the presence of 1 microM-isoprenaline, insulin was less effective in stimulating glucose phosphorylation and glycogen synthesis. The stimulation of glycogenolysis by isoprenaline was only slightly decreased even at high (10000 microunits/ml) concentrations of insulin. Insulin-stimulated phosphorylation of 2-deoxyglucose was decreased by isoprenaline. It is suggested that this decrease in the rate of glucose phosphorylation is caused by the observed elevated concentration of glucose 6-phosphate, which inhibits hexokinase activity. This conclusion is supported by the fact that isoprenaline had no effect on the stimulation of 3-O-methylglucose transport by insulin.

scholarly journals Sensitivity to insulin of glycolysis and glycogen synthesis of isolated soleus-muscle strips from sedentary, exercised and exercise-trained rats

1983 ◽  
Vol 212 (2) ◽  
pp. 453-458 ◽  
Author(s):  
J Espinal ◽  
G L Dohm ◽  
E A Newsholme
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Tolerance ◽  
Soleus Muscle ◽  
Glycogen Synthesis ◽  
Treadmill Training ◽  
Insulin Concentration ◽  
Maximal Stimulation ◽  
Stimulation Of

The half-maximal stimulation of the rates of glycolysis and glycogen synthesis in soleus-muscle strips from sedentary animals occurred at a concentration of insulin of about 100 microunits/ml. In soleus-muscle strips from exercise-trained rats (5 weeks of treadmill training), half-maximal stimulation of the rate of glycolysis occurred at about 10 microunits of insulin/ml, whereas that for glycogen synthesis occurred between 10 and 100 microunits of insulin/ml. The sensitivity of glycolysis to insulin after exercise training is similar to that of adipose tissue from sedentary animals. This finding suggests that, in sedentary animals, the effects of normal changes in insulin concentration may affect muscle primarily indirectly via the anti-lipolytic effect on adipose tissue, whereas after training insulin may effect the rate of glycolysis in muscle directly. A single period of exercise did not change the sensitivity of glycolysis in soleus muscle to insulin, nor probably that of glycogen synthesis. It is suggested that the improvement in insulin sensitivity of glycolysis in muscle caused by exercise-training could account, in part, for the well-established improvement in glucose tolerance and insulin sensitivity observed in man and rats after exercise-training.

scholarly journals β-adrenoceptor-agonist and insulin actions on glucose metabolism in rat skeletal muscle in different thyroid states

1991 ◽  
Vol 278 (2) ◽  
pp. 587-593 ◽  
Author(s):  
G D Dimitriadis ◽  
S J Richards ◽  
M Parry-Billings ◽  
B Leighton ◽  
E A Newsholme ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Adenylate Cyclase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Beta Adrenoceptor ◽  
Adrenoceptor Agonist ◽  
Lactate Formation

1. The actions of the beta-adrenoceptor agonist isoprenaline on glucose and glycogen metabolism, in the presence of various concentrations of insulin, were investigated in isolated soleus muscle preparations taken from eu-, hyper- and hypothyroid rats. 2. Hyperthyroidism, induced by 3,3′,5-tri-iodo-D-thyronine (T3) administration for 5 days, increased the rate of lactate formation and suppressed the rate of glycogen synthesis in soleus muscle in response to isoprenaline, even in the presence of physiological or supraphysiological insulin concentrations. 3. Hypothyroidism, induced by administration of 6-n-propyl-2-thiouracil for 4 weeks, decreased the rate of isoprenaline-stimulated lactate formation at all insulin concentrations, but significantly decreased the responsiveness of lactate formation only at low insulin concentrations. In the presence of 100 or 10,000 mu-units of insulin/ml, the ability of isoprenaline to suppress the rate of glycogen synthesis was markedly impaired (inhibition at 100 mu-units of insulin/ml and 1 micro-M-isoprenaline: eu- 72.6 +/- 2.9%; hypo-41.0 +/- 2.1%; P less than 0.001). 4. Hyperthyroidism had no effect on the number or affinity of beta-adrenoceptors, defined by 125I-pindolol binding, or beta-adrenoceptor- or forskolin-stimulated adenylate cyclase activity in membrane preparations of gastrocnemius muscle, whereas hypothyroidism increased the beta-adrenoceptor density and decreased the beta-adrenoceptor-stimulated adenylate cyclase activity, without affecting the receptor affinity or forskolin-stimulated adenylate cyclase activity. 5. It is concluded that there is a complex interplay between insulin, catecholamines and thyroid hormones to regulate skeletal-muscle glucose metabolism. The changes observed in muscles in hypothyroidism may be explained, at least in part, by changes in beta-adrenoceptor-G-protein-adenylate cyclase coupling affecting the generation of cyclic AMP and the regulation of some of the key enzymes of glycogen metabolism; in contrast, the changes observed in muscles in hyperthyroidism do not appear to result from alterations at the level of the receptor-mediated second-messenger generation.

scholarly journals Effects of dexamethasone treatment on insulin-stimulated rates of glycolysis and glycogen synthesis in isolated incubated skeletal muscles of the rat

1987 ◽  
Vol 246 (2) ◽  
pp. 551-554 ◽  
Author(s):  
B Leighton ◽  
R A J Challiss ◽  
F J Lozeman ◽  
E A Newsholme
Keyword(s):  
Soleus Muscle ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Glycogen Synthesis ◽  
Extensor Digitorum Longus Muscle ◽  
Extensor Digitorum ◽  
Hexose Transport ◽  
Dexamethasone Treatment ◽  
Longus Muscle ◽  
Lactate Formation

1. Rats were treated with dexamethasone for 4 days before measurement of the rates of lactate formation [which is an index of hexose transport; see Challiss, Lozeman, Leighton & Newsholme (1986) Biochem. J. 233, 377-381] and glycogen synthesis in response to various concentrations of insulin in isolated incubated soleus and extensor digitorum longus muscle preparations. 2. The concentration of insulin required to stimulate these processes half-maximally in soleus and extensor digitorum longus muscles isolated from control rats was about 100 muunits/ml. 3. Dexamethasone increases the concentration of insulin required to stimulate glycolysis half-maximally in soleus and extensor digitorum longus preparations to 250 and 300 muunits/ml respectively. The respective insulin concentrations necessary to stimulate glycogen synthesis half-maximally were about 430 and 370 muunits/ml for soleus and extensor digitorum longus muscle preparations isolated from steroid-treated rats. 5. Dexamethasone treatment did not change the amount of insulin bound to soleus muscle.

scholarly journals Beta-adrenoceptor agonist stimulation of pulmonary nitric oxide production in the rabbit

1999 ◽  
Vol 126 (3) ◽  
pp. 833-839 ◽  
Author(s):  
L Christofer Adding ◽  
Per Agvald ◽  
Andreas Artlich ◽  
Magnus G Persson ◽  
Lars E Gustafsson
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Production ◽  
Beta Adrenoceptor ◽  
Oxide Production ◽  
Agonist Stimulation ◽  
Adrenoceptor Agonist ◽  
Stimulation Of

scholarly journals Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat

1989 ◽  
Vol 257 (2) ◽  
pp. 369-373 ◽  
Author(s):  
G D Dimitriadis ◽  
B Leighton ◽  
M Parry-Billings ◽  
D West ◽  
E A Newsholme
Keyword(s):  
Fatty Acids ◽  
Glucose Metabolism ◽  
Free Fatty Acids ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Plasma Levels ◽  
Glucose Oxidation ◽  
Glycogen Synthesis ◽  
Fasting Plasma ◽  
Glucose Phosphorylation

1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations.

scholarly journals Effects of hyperthyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat

1988 ◽  
Vol 253 (1) ◽  
pp. 87-92 ◽  
Author(s):  
G D Dimitriadis ◽  
B Leighton ◽  
I G Vlachonikolis ◽  
M Parry-Billings ◽  
R A J Challiss ◽  
...  
Keyword(s):  
Soleus Muscle ◽  
Glucose Oxidation ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Plasma Concentrations ◽  
Glucose Disposal ◽  
Increased Sensitivity ◽  
Glucose Phosphorylation ◽  
Gastrocnemius Muscles ◽  
Glycogen Breakdown

1. The effects of hyperthyroidism on the sensitivity and responsiveness of glycolysis and glycogen synthesis to insulin were investigated in the isolated incubated soleus muscle of the rat. 2. Hyperthyroidism, which was induced by administration of tri-iodothyronine (T3) to rats for 2, 5 or 10 days, increased fasting plasma concentrations of glucose, insulin and free fatty acids. 3. Administration of T3 for 2 or 5 days increased the rates of glycolysis at all insulin concentrations studied: this was due to increased rates of both glucose phosphorylation and glycogen breakdown, but there was no effect of T3 on the sensitivity of glycolysis to insulin. However, administration of T3 for 10 days increased the sensitivity of the rate of glycolysis to insulin. 4. The concentration of adenosine in the gastrocnemius muscles of the rats was not different from controls after 5 days, but it was markedly decreased after 10 days of T3 administration. If these changes are indicative of changes in the soleus muscle, the increased sensitivity of glycolysis to insulin found after 10 days′ T3 administration could be due to the decrease in the concentration of adenosine. 5. Administration of T3 decreased the sensitivity of glycogen synthesis to insulin and the glycogen content of the soleus muscles. This may explain the decreased rates of non-oxidative glucose disposal found in spontaneous and experimental hyperthyroidism in man. 6. The rates of glucose oxidation did not change after 2 days, but they were increased after 5 and 10 days of T3 administration.

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong
Keyword(s):  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Adrenoceptor Antagonist ◽  
Cardiac Contractile ◽  
Plasmic Reticulum ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
Stimulation Of

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.

Properties of a T-Type Ca2+Channel–Activated Slow Afterhyperpolarization in Thalamic Paraventricular Nucleus and Other Thalamic Midline Neurons

2009 ◽  
Vol 101 (6) ◽  
pp. 2741-2750 ◽  
Author(s):  
Li Zhang ◽  
Leo P. Renaud ◽  
Miloslav Kolaj
Keyword(s):  
Information Transfer ◽  
Brain Slice ◽  
Calcium Concentration ◽  
Channel Blockers ◽  
Thalamic Neurons ◽  
Adrenoceptor Agonist ◽  
Report Data ◽  
Low Threshold ◽  
Rat Brain Slice ◽  
Stimulation Of

Burst firing mediated by a low-threshold spike (LTS) is the hallmark of many thalamic neurons. However, postburst afterhyperpolarizations (AHPs) are relatively uncommon in thalamus. We now report data from patch-clamp recordings in rat brain slice preparations that reveal an LTS-induced slow AHP (sAHP) in thalamic paraventricular (PVT) and other midline neurons, but not in ventrobasal or reticular thalamic neurons. The LTS-induced sAHP lasts 8.9 ± 0.4 s and has a novel pharmacology, with resistance to tetrodotoxin and cadmium and reduction by Ni2+ or nominally zero extracellular calcium concentration, which also attenuate both the LTS and sAHP. The sAHP is inhibited by 10 mM intracellular EGTA or by equimolar replacement of extracellular Ca2+ with Sr2+, consistent with select activation of LVA T-type Ca2+ channels and subsequent Ca2+ influx. In control media, the sAHP reverses near EK+, shifting to −78 mV in 10.1 mM [K+]o and is reduced by Ba2+ or tetraethylammonium. Although these data are consistent with opening of Ca2+-activated K+ channels, this sAHP lacks sensitivity to specific Ca2+-activated K+ channel blockers apamin, iberiotoxin, charybdotoxin, and UCL-2077. The LTS-induced sAHP is suppressed by a β-adrenoceptor agonist isoproterenol, a serotonin 5-HT7 receptor agonist 5-CT, a neuropeptide orexin-A, and by stimulation of the cAMP/protein kinase A pathway with 8-Br-cAMP and forskolin. The data suggest that PVT and certain midline thalamic neurons possess an LTS-induced sAHP that is pharmacologically distinct and may be important for information transfer in thalamic–limbic circuitry during states of attentiveness and motivation.

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