Abstract:
:1. Use of the antihyperglycaemic agent, metformin, is often associated with a small rise in circulating lactate. This study investigates the source of the lactate and examines the effect of metformin on glucose metabolism by the intestine and liver of rats. 2. Changes in plasma glucose and lactate were measured in the inferior vena cava (IVC), hepatic portal vein (HPV), hepatic vein (HV) and aorta (A) after intrajejunal administration of metformin (50 and 250 mg kg-1) without and with glucose (2 g kg-1). 3. Metformin 250 mg kg-1 reduced the hyperglycaemic response to a glucose challenge, associated with a greater reduction of glucose concentrations in the HPV (average decrease of 33% at 60 and 120 min) than at other sites. 4. Both doses of metformin increased lactate concentrations in the glucose-loaded state: the highest concentration (2.5 fold increase) was recorded in the HPV 60 min after administration of 250 mg kg-1 metformin, with a high lactate concentration persisting in the HV at 120 min. Metformin 250 mg kg-1 also increased lactate concentrations in the basal state, with highest concentrations (2 fold increase) in the HPV. 5. Two hours after intrajejunal administration of metformin, 50 mg kg-1, rings of tissue from the small intestine showed an average 22% decrease in glucose oxidation ([14C]-glucose conversion to 14CO2) and a 10% increase in lactate production. Since glucose metabolism in the gut is predominantly anaerobic, metformin caused an overall 9.5% increase of intestinal glucose utilization.6. Metformin, 10-6 and I0- mol 1', did not significantly alter glucose oxidation or lactate production by isolated hepatocytes, but a very high concentration of metformin (102 mol 1') increased lactate production by 60%.7. The results support the view that metformin increased intestinal glucose utilization and lactate production by the intestine. Under basal conditions there was net extraction of lactate by the liver but not after an enteral glucose load.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Bailey CJ,Wilcock C,Day Cdoi
10.1111/j.1476-5381.1992.tb09093.xsubject
Has Abstractpub_date
1992-04-01 00:00:00pages
1009-13issue
4eissn
0007-1188issn
1476-5381journal_volume
105pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:5-HT receptor agonists have variable nociceptive effects within the spinal cord. While there is some evidence for 5-HT(1A) spinally-mediated analgesia, the role of other 5-HT(1) receptor subtypes remains unclear. In the present study, we examined the spinal actions of a range of 5-HT(1) agonists,...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01685.x
更新日期:2012-03-01 00:00:00
abstract::GR231118 (also known as 1229U91 and GW1229), a purported Y(1) antagonist and Y(4) agonist was radiolabelled using the chloramine T method. [(125)I]-GR231118 binding reached equilibrium within 10 min at room temperature and remained stable for at least 4 h. Saturation binding experiments showed that [(125)I]-GR231118 b...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702983
更新日期:2000-01-01 00:00:00
abstract::1. Conscious normotensive cynomolgus monkeys were chronically instrumented for the measurement of arterial blood pressure and heart rate to investigate the relationships between the plasma concentration, suppression of the pressor response to angiotensin II (AII), compensatory increase in plasma AII, and hypotensive e...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb14036.x
更新日期:1994-01-01 00:00:00
abstract::1. Gastric acid secretory responses to pentagastrin were characterized in the rat isolated gastric mucosa. In particular, the mechanisms underlying fade, declining response upon continued stimulation, and tachyphylaxis, progressively reduced responses upon repeated stimulation, were investigated. 2. Pentagastrin, 10(-...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11738.x
更新日期:1988-12-01 00:00:00
abstract::1. The purpose of the present investigations was to determine the influence of increasing age on the pharmacokinetics and pharmacodynamics of midazolam in male BN/BiRij rats as an animal model of aging. 2. Midazolam was administered intravenously at a dose of 2.5 mg kg-1 and its pharmacokinetics were determined on the...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14482.x
更新日期:1992-09-01 00:00:00
abstract::Forty-eight isolated rat hearts were perfused with Krebs solution and with [(3)H]-(-)-noradrenaline ([(3)H]-NA) containing 4.5 nCi/ml in 50 ng/ml, as described by Iversen (1963). To groups of six, cocaine was added to [(3)H]-NA in concentrations of 400 nM, 2 and 10 muM. To the rest Tween 80, 25 mug/ml was added to [(3...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb10686.x
更新日期:1974-07-01 00:00:00
abstract::1. The effect of the A2A adenosine receptor agonist, 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS 21680) on the potassium evoked release of [3H]-gamma-aminobutyric acid ([3H]-GABA) from nerve terminals derived from the caudate-putamen and the globus pallidus of the rat was compared. In both ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb16171.x
更新日期:1994-09-01 00:00:00
abstract::The endogenous concentrations of p- and m-hydroxyphenylacetic acid in the mouse caudate nucleus were determined by a gas chromatographic or a gas chromatographic-mass spectrometric technique and the concentrations were about 30 and 11 ng g-1 respectively. The subcutaneous administration of (+)-butaclamol (1 mg kg-1), ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10732.x
更新日期:1983-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:While remifentanil can be used either during labour or fetal surgery, more should be known about the transplacental transfer of this opioid. The aim of this study was to investigate the placental transfer and haemodynamic effects of remifentanil after i.v. administration to pregnant ewes. EXPERI...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00783.x
更新日期:2010-12-01 00:00:00
abstract::1. The hyperpolarization of the resting membrane potential, Vm, induced by isoprenaline in the lumbrical muscle fibres of the mouse, was investigated by use of intracellular microelectrodes. 2. In normal Krebs-Henseleit solution (potassium concentration: K+o = 5.7 mM, 'control'), Vm was -7.40 +/- 0.2 mV; lowering K+o ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15940.x
更新日期:1995-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Animal models of drug-seeking suggest that exposure to cues associated with self-administered drugs and drug primes might precipitate relapse via activation of central dopaminergic substrates. EXPERIMENTAL APPROACH:The effects of priming injections of dopamine and 5-HT agonists on drug-seeking a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.01193.x
更新日期:2011-04-01 00:00:00
abstract::1 Poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme activated by strand breaks in DNA, which are caused by reactive oxygen species (ROS). Here we investigate the effects of the PARS inhibitors 3-aminobenzamide (3-AB), nicotinamide and 1,5-dihydroxyisoquinoline (ISO) on the circulatory failure and the organ injur...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702928
更新日期:1999-11-01 00:00:00
abstract::1. The effects of flecainide alone, mexiletine alone and their combination at the Na+ channel level were studied in guinea-pig papillary muscles. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the fast inward Na+ current (INa). 2. In muscles driven at 0.02 Hz, neither mexiletine...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb09803.x
更新日期:1991-06-01 00:00:00
abstract::Botulinum toxin (Type A) depressed or abolished transmission from postganglionic nerves to smooth muscle of isolated preparations of guinea-pig and mouse vas deferens. The time course of blockade was 2 to 6 times slower than that observed with the same concentration of the same batch of toxin on the rat diaphragm. Spo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08343.x
更新日期:1973-02-01 00:00:00
abstract::1. Intrathecal (i.t.) administration of nociceptin and high doses of morphine induced allodynia in response to innocuous tactile stimuli, and i.t. nociceptin evoked hyperalgesia in response to noxious thermal stimuli in conscious mice. Here we have characterized the nociceptin-induced allodynia and compared it with th...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701146
更新日期:1997-06-01 00:00:00
abstract::We have demonstrated previously that infusion of angiotensin II (AngII) into hyperlipidemic mice augments atherosclerosis and results in the formation of abdominal aortic aneurysms (AAA). The purpose of this study was to determine the role of aldosterone in these AngII-induced vascular pathologies. Male apolipoprotein...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706098
更新日期:2005-02-01 00:00:00
abstract::1 Weighed stripped vasa deferentia were incubated in Holman's solution containing (a) [14C]-sorbitol 0.014 mm, (b) [3H]-noradrenaline ([3H]-NA) 12.31 nM, (c) [3H]-tetrahydrocannabinol ([3H]-delta1-THC) 1 mug/ml for 5, 10, 20 and 30 minutes. 2 Tissues were washed, dissolved in Protosol, counted by standard scintillatio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07451.x
更新日期:1976-04-01 00:00:00
abstract::1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic anta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703301
更新日期:2000-05-01 00:00:00
abstract::1. The effect of adenosine triphosphate (ATP) and its stable analogues, alpha, beta-methylene-ATP and beta, gamma-methylene-ATP, on the efferent function of capsaicin-sensitive non-adrenergic, non-cholinergic (NANC) nerves was tested in guinea-pig isolated atria. 2. Transmural nerve stimulation of atria isolated from ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb09011.x
更新日期:1992-03-01 00:00:00
abstract::1. In this study, we investigated the effects of different drugs (a kappa-opioid receptor agonist U-50,488, a vasopressin receptor antagonist dPTyr(Me)AVP or an N-methyl-D-aspartate (NMDA) receptor antagonist MK-801) on the development of morphine tolerance in rat hippocampal slices. 2. Hippocampal slices (450 microm)...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701646
更新日期:1998-02-01 00:00:00
abstract::Hind paw oedema in rats, measured by plethysmography or extravasation of Evans Blue dye into the skin, after subplantar injection of submaximal doses of carrageenin (1-100 micrograms) was significantly increased for 4 h during kininase II inhibition with captopril (1 mg kg-1, s.c.). Submaximal oedema, as assessed by p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16435.x
更新日期:1984-05-01 00:00:00
abstract::1 The effects of opioids on synaptic transmission in cat sacral parasympathetic colonic ganglia were studied in vitro, using intracellular electrophysiological techniques. Electrical stimulation of the pelvic nerve evoked fast excitatory postsynaptic potentials (e.p.s.ps), which were blocked by hexamethonium and tetro...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb11340.x
更新日期:1987-10-01 00:00:00
abstract::1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a hyperpolarization-activated current If. A hyperpolarization-activated current Ih, which is present in many types of neu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702153
更新日期:1998-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain. EXPERIMENTAL APPROACH:Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13470
更新日期:2016-05-01 00:00:00
abstract::A study has been made of the pharmacology of the 5-hydroxytryptamine (5-HT)-induced depolarization responses that can be recorded extracellularly from the rat isolated cervical vagus nerve. Phenylbiguanide (PBG) and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) were found to mimic the effects of 5-HT on the vagus nerve...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb16844.x
更新日期:1987-01-01 00:00:00
abstract::1. Bradykinin (BK) and Lys-BK are peptides which are released at high nanomolar concentrations into the tear-film of ocular allergic patients. We hypothesized that these peptides may activate specific receptors on the ocular surface, especially the corneal epithelium (CE) and thus the CE cells may represent a potentia...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701168
更新日期:1997-06-01 00:00:00
abstract::1. Neurally-evoked output of newly synthesized [3H]-acetylcholine from the rat phrenic nerve was measured in the absence of cholinesterase inhibitors. 2. Noradrenaline and isoprenaline enhanced neurally-evoked transmitter output markedly. Moreover, immediately after the application of noradrenaline the basal tritium e...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11574.x
更新日期:1988-07-01 00:00:00
abstract::1. This study compares a cyclo-oxygenase inhibitor (aspirin), a 5-HT2 antagonist (ZM170809) and a combined thromboxane synthase inhibitor/receptor antagonist (ZD1542) as adjuncts to tissue plasminogen activator (rt-PA). 2. Application of an anodal current (332 +/- 4.1 microA) to the stenosed left circumflex coronary a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb13063.x
更新日期:1994-05-01 00:00:00
abstract::In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic,...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0706638
更新日期:2006-02-01 00:00:00
abstract::Melatonin deprival in young rats induces alterations in cerebral arteriolar wall similar to those observed during aging: atrophy and a decrease in distensibility. In this study, we examined the effects of melatonin treatment on cerebral arteriolar structure and distensibility and on the lower limit of cerebral blood f...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0705629
更新日期:2004-02-01 00:00:00