Abstract:
:1. The recognition of the role of insulin resistance in disease states and the recent development of new drugs that modify insulin-dependent metabolism has led to increased use of the euglycaemic hyperinsulinaemic clamp to measure in vivo insulin sensitivity, but several key aspects of the technique are poorly documented in the literature. 2. We have evaluated the reproducibility and intersubject variation of measurements of insulin sensitivity in groups of insulin-sensitive and insulin-resistant subjects and assessed the effects of hand warning on haemodynamic and metabolic responses. 3. Subjects participated in one of two protocols: (i) 18 healthy male volunteers and 18 patients with hypertension and glucose intolerance were clamped on two occasions, 1 week apart with measurements of insulin sensitivity (M) derived after 120 and 180 min of hyperinsulinaemia; and (ii) six healthy volunteers were clamped on one occasion with simultaneous sampling of antecubital and 'arterialized' (dorsal hand) venous blood for comparison of plasma glucose concentrations and oxygen saturation and a further six volunteers were clamped on two occasions with and without the use of hand warming. 4. Measurements of M derived after 120 min (M120) and 180 min (M180) of hyperinsulinaemia were reproducible: the coefficients of repeatability (mg/kg per min) of M120 and M180 were 1.0 and 0.9 for volunteers and 1.0 and 1.0 for the patient group, respectively. The intersubject variation in insulin stimulus was high: coefficients of variation for M180 were 22% for volunteers compared with 38% for the patient group. In volunteers compared with the patient group, hand warming significantly increased venous oxygen saturations (95 +/- 2 vs 79 +/- 18%, respectively) and glucose concentrations (5.2 +/- 0.2 vs 4.5 +/- 0.4 mmol/L, respectively) and measurements of M were significantly higher using arterialized compared with antecubital venous blood. However, local hand warming was associated with systemic vasodilatation: blood pressure decreased (e.g. 6 mmHg diastolic; P < 0.05) with a compensatory increase in heart rate (8 b.p.m.). 5. In conclusion, clamps of 120 and 180 min duration yielded measurements of M that were reproducible. The technique is much more robust when used in the context of a crossover design because of the significant (20-40%) intersubject variation in M, even among apparently homogeneous male volunteers. Hand warming effectively arterializes venous blood and gives significantly higher M values, but induces systemic vasodilation, which may confound measurements of M.
journal_name
Clin Exp Pharmacol Physioljournal_title
Clinical and experimental pharmacology & physiologyauthors
Morris AD,Ueda S,Petrie JR,Connell JM,Elliott HL,Donnelly Rdoi
10.1111/j.1440-1681.1997.tb01237.xsubject
Has Abstractpub_date
1997-07-01 00:00:00pages
513-8issue
7eissn
0305-1870issn
1440-1681journal_volume
24pub_type
杂志文章abstract::1. To elucidate the physiological role of nitric oxide (NO) in regulating vascular tone, the effects of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, on the vasoconstrictor response to noradrenaline (NA) in rat caudal artery was examined. 2. NG-Nitro-L-arginine methyl ester significantly potenti...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.1999.03062.x
更新日期:1999-05-01 00:00:00
abstract::1. Conscious experimental hypertensive rats injected intraventricularly with 5,6-dihydroxytryptamine (50 microgram) responded with a rapid and long-lasting (4 days) fall in blood pressure and this was accompanied by a bradycardia of similar duration. 2. The acute actions of 5,6-dihydroxytryptamine on the cardiovascula...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1975.tb01855.x
更新日期:1975-11-01 00:00:00
abstract::1. The hepatic reticulo-endothelial cell population is generally assumed to increase in size, along with the liver, during ageing in rats. However, this has not been rigorously established. 2. Using electron microscopy and stereological techniques, the present study has shown that the volume densities of hepatocytes a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1992.tb00501.x
更新日期:1992-07-01 00:00:00
abstract::1. Nineteen-day old rats were fed an essential fatty acid deficient diet for 37 weeks, thereby making them essential fatty acid deficient for at least 24 weeks. The weights of their brains were 33% less than those of rats on control diets. 2. When the deficient rats were rehabilitated for ten weeks on a diet containin...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1979.tb00022.x
更新日期:1979-07-01 00:00:00
abstract::1. In order to further characterize the adenosine binding sites that we previously purified and termed P3 purinergic receptor-like protein (P3LP), a reliable binding assay method was developed using [3H]-5'-N-ethylcarboxamidoadenosine (NECA) as a radioligand and the newly developed high-affinity selective ligand 9-(6,...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2001.03438.x
更新日期:2001-04-01 00:00:00
abstract::Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin recepto...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/1440-1681.12688
更新日期:2017-01-01 00:00:00
abstract::1. Despite the array of sophisticated imaging techniques available for biological applications, none of the standard biomedical techniques adequately provides the capability to measure motion and flow. Those techniques currently in use are particularly lacking in spatial and temporal resolution. 2. Herein, we introduc...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05102.x
更新日期:2009-02-01 00:00:00
abstract::1. The reproducibility of blood volume measurements, using [51Cr]-labelled red blood cells (RBC) was tested in three lambs, 79-89 days of age, and the accuracy was tested in eight lambs, 83 +/- 0.4 days of age, in which blood volume was measured simultaneously by [51Cr]-RBC and [125I]-gamma globulin plus haematocrit (...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02557.x
更新日期:1994-07-01 00:00:00
abstract::1. The effects of ouabain and acetazolamide on the secretion of pancreatic juice stimulated by secretin in anaesthetized dogs were investigated. 2. Intra-arterial injection of ouabain (1-10 micrograms) and acetazolamide (1-10 mg) caused dose-dependent decreases in the volume of pancreatic juice. When both drugs were a...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1989.tb01538.x
更新日期:1989-03-01 00:00:00
abstract::1. Carbachol (CCh)-induced desensitization to CCh was interrupted by a transient resensitization during its early stage, with concomitant changes at the muscarinic receptor/G-protein level in smooth muscle of guinea-pig taenia caeci. To assess whether such a peculiar desensitizing process may heterologously regulate s...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2007.04530.x
更新日期:2007-01-01 00:00:00
abstract::1. In the present study, we examined whether the nuclear transcription factor (NF)-kappaB activity plays a role in the determination of sensitivity to tumour necrosis factor (TNF)-alpha or agonistic Fas antibody (Ab) in human vascular smooth muscle cells (hVSMC). 2. To inhibit agonist-induced NF-kappaB activation in h...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2003.03817.x
更新日期:2003-03-01 00:00:00
abstract::MicroRNA plays an integral role in the development of atherosclerosis. Our study aimed to investigate the roles of miR-599 in lipopolysaccharide (LPS)-induced endothelial damage in human umbilical vein endothelial cells (HUVECs). HUVECs were transfected with a miR-599 mimic and negative control, and then exposed to LP...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13316
更新日期:2020-08-01 00:00:00
abstract::1. Protease-activated receptor 2 (PAR2), present in capsaicin-sensitive sensory neurons, induces gastric mucus secretion and mucosal cytoprotection. 2. We studied the possible cross-talk between PAR2 and vanilloid receptor 1 (VR1). The VR1 antagonist capsazepine partially inhibited the PAR2-mediated increase in gastri...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.2002.03641.x
更新日期:2002-04-01 00:00:00
abstract::1. Anoxic perfusion of the isolated rat heart releases noradrenaline in the absence of sympathetic nerve fibre stimulation. 2. Anoxic noradrenaline release is enhanced by reducing the extracellular Na+ concentration, consistent with the proposal that such release occurs by carrier-mediated efflux. 3. Release is also e...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1991.tb01375.x
更新日期:1991-01-01 00:00:00
abstract::Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus (NDV) represents an attractive ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.2011.05662.x
更新日期:2012-08-01 00:00:00
abstract::Severe drug eruption (SDE), a common skin disease, becomes dangerous when it occurs in patients with human immunodeficiency virus (HIV). However, the molecular mechanisms are poorly understood. Forty patients including HIV+ SDE+ (n = 15), HIV- SDE+ (n = 15) and HIV+ SDE- (n = 10) subjects were enrolled in our study. A...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13266
更新日期:2020-06-01 00:00:00
abstract::1. The effects of endogenous and exogenous acetylcholine (ACh) on nitrergic relaxations elicited by electrical field stimulation (EFS) were studied in guinea-pig endothelium-denuded basilar artery preparations precontracted with 1 mumol/L prostaglandin F2 alpha and a possible role of K+ channels in mediating the effec...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::1. The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon-like peptide-1 (GLP-1), with regard to brain prostanoids, in urethane-anaesthetized rats. 2. Glucagon-like peptide-1 and other compounds were administered intracerebroventricularly (i.c.v....
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.04957.x
更新日期:2008-08-01 00:00:00
abstract::1. The aim of the present study was to evaluate the usefulness and reliability of a portable indirect calorimeter (Metavine; Vine, Tokyo, Japan). 2. We measured energy expenditure (EE) of elderly people (n = 191) at nursing homes using both Metavine and an authorized indirect calorimeter (Deltatrac Metabolic Monitor; ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1046/j.1440-1681.29.s4.6.x
更新日期:2002-10-01 00:00:00
abstract::Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studi...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/1440-1681.13020
更新日期:2019-01-01 00:00:00
abstract::1. The diffusional permeability of collecting ducts to 22Na+ and 36Cl- was measured in rat papillae in vitro. 2. The permeability of the collecting duct to 36Cl- was 0.72 (s.e.m. = 0.01; n = 356) microns/sec which was significantly higher than the value of 0.51 (s.e.m. = 0.01; n = 356) microns/sec measured for 22Na+. ...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1982.tb00837.x
更新日期:1982-11-01 00:00:00
abstract::1. The low molecular weight heparin (LMWH) dalteparin is used, for example, to prevent primary venous thromboembolism in patients undergoing surgery or in medically ill patients. The anticoagulant activity of dalteparin can be monitored by measuring anti-factor Xa levels and activated partial thromboplastin time (aPTT...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2011.05593.x
更新日期:2011-11-01 00:00:00
abstract::1. Chromium picolinate (CrPic) has been recommended as an alternative therapeutic regimen for Type 2 diabetes mellitus (T2DM). However, the molecular mechanism underlying the action of CrPic is poorly understood. 2. Using normal and insulin-resistant 3T3-L1 adipocytes, we examined the effects of CrPic on the gene tran...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2009.05164.x
更新日期:2009-08-01 00:00:00
abstract::1. The aim of the present study was to examine the effect of bacterial lipopolysaccharide (LPS) on the disposition of an organic anion transporting polypeptide and P-glycoprotein substrate in the rat isolated perfused liver. 2. Male Sprague-Dawley rats were divided into four groups. Three of the groups received 1, 2.5...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2006.04419.x
更新日期:2006-08-01 00:00:00
abstract::Serotonin causes a dose related (0.1-20 micrograms/kg i.v.) increase in mean arterial blood pressure (MAP) and heart rate in conscious sheep. Ketanserin (0.1 mg/kg per h i.v.) causes a decrease in blood pressure, and an increase in heart rate. In the presence of ketanserin, serotonin induced increases in MAP are atten...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1984.tb00872.x
更新日期:1984-11-01 00:00:00
abstract::1. Intravenous endothelin-1 releases endothelium-derived relaxing factor (EDRF) and prostacyclin from the lungs, and substantial pulmonary clearance is claimed. Since these vaso-active substances could alter the haemodynamic effects of endothelin-1, the effects of boluses of endothelin-1 injected intravenously and int...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.1994.tb02521.x
更新日期:1994-04-01 00:00:00
abstract::1. Erlotinib, a small-molecule epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor, has been approved for the management of advanced non-small cell lung cancer. The aim of the present study was to investigate whether erlotinib exerts potent antitumour activities through the reactive oxygen species (RO...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2008.05091.x
更新日期:2009-05-01 00:00:00
abstract::1. Mathematical modelling is useful in pharmacology, allowing the investigator to obtain insights into the biological processes under study that may not always be intuitively obvious. Examples are presented in this review using the pharmacology of the muscarinic acetylcholine receptor (mAChR) agonist xanomeline. 2. Xa...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1681.2001.03376.x
更新日期:2001-03-01 00:00:00
abstract::1. Initial unsuccessful attempts to evaluate ventricular function in terms of the 'heart as a pump' led to focusing on the 'heart as a muscle' and to the concept of myocardial contractility. However, no clinically ideal index exists to assess the contractile state. The aim of the present study was to develop a mathema...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章
doi:10.1111/j.1440-1681.2010.04282.x
更新日期:2005-10-01 00:00:00
abstract::1. Direct cortical stimulation of motor and sensory areas of the cortex in experimental animals and some neurosurgical patients has provided much useful physiological information. Some of the benefits of this approach can be provided in awake volunteer subjects using new techniques which activate the motor cortex thor...
journal_title:Clinical and experimental pharmacology & physiology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1681.1996.tb01148.x
更新日期:1996-10-01 00:00:00