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At least 1,369 records · Page 76Linked to original sources
PubMed1997

Anxiolytic activity of glycine-B antagonists and partial agonists--no relation to intrinsic activity in the patch clamp.

On the basis of animal models, anxiety was one of the first suggested clinical applications of partial agonists of the glycineB site coupled to the NMDA receptor. It is not certain, however, whether these findings can be extended to full glycineB antagonists and what is the relation between intrinsic activity (degree of NMDA receptor antagonism) and anxiolytic effect. In the present study several NMDA receptor antagonists, including several glycineB antagonists/partial agonists, were tested for anxiolytic activity in the Vogel conflict test and the elevated plus-maze. Additionally, the intrinsic activities of the glycineB partial agonists used [ACPC, (R,+)-HA-966 and D-cycloserine] were compared in patch-clamp experiments in cultured neurones. In the plus-maze the most striking increase in the time spent in open arms (index of anxiolytic effect) was seen after diazepam and D-cycloserine (at doses that did not change locomotion). Also reliable (dose-dependent), although weaker, anxiolytic activity was produced by the uncompetitive NMDA receptor antagonist (+)MK-801 and the competitive antagonist CGP 39551. Modest anxiolytic-like effect in the plus-maze was also observed after the glycineB antagonist L-701,324 and the partial agonist (+,R)-HA-966. Uncompetitive antagonists memantine and amantadine, the glycineB partial agonist ACPC (up to 600 mg/kg) or the full antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 had no effect. In the Vogel conflict test neither memantine, nor any of the full glycineB antagonists tested (L-701,324 and MRZ 2/576), showed anxiolytic activity. Patch-clamp studies revealed that the intrinsic activity of (+,R)-HA-966, D-cycloserine and ACPC was 13, 57 and 92%, respectively, as compared to that of glycine itself (100%). In conclusion, for the agents tested there is no clear relation between the levels of intrinsic activity, i.e. degree of NMDA receptor inhibition, and anxiolytic activity. Moreover, L-701,324 and MRZ-type glycineB full antagonists do not exchibit anxiolytic activity in the elevated plus-maze and Vogel conflict test.

Animals↗
PubMed1998

Double-vein jugular/inferior vena cava clamp technique for long-term in vivo studies in rats.

We present a step-by-step manual for chronic cannulation of rats using a simple technique. This concept facilitates repeated clamping of the same rat over a 6-10-week period, providing a completely separate infusion route from blood sampling access which is placed into mixed venous blood in the inferior vena cava. Permanent catheters implanted into the left external jugular vein and the inferior vena cava were used for miniature blood sampling and recycling. The design and running of clamp experiments and other physiological research models are detailed. Long-term reliable venous access, simple installation, and easy after-care of the rats' cannulas are the principal advantages of the procedure described.

Animals↗
PubMed1998

Cut-open oocyte voltage-clamp technique.

In this article, we described the use and limitations of the COVG technique. The advantages of the present method as follows: 1. High-frequency response and low noise recording (24-microseconds time constant and 1.2-nA rms at 5 kHz). This allows the accurate description of small gating currents and fast activation or deactivation of ionic currents to be adequately resolved. Currents up to 20-30 microA can be adequately clamped. 2. Stable recording conditions lasting for several hours. Even though this technique has internal access, rundown is minimized compared to excised patches. 3. Access to the cell interior. The intracellular medium can be exchanged with various solutions. This was of invaluable help in recording K+ gating currents, an experimental condition that required the complete blockade of all ionic currents. This advantage will make the present method suitable for the study of channel modulation by second messengers and drugs. In addition, channel selectivity properties can be defined by ion substitution experiments. 4. Channel localization. A study of the membrane compartmentalization of channels can be easily obtained with this method, since it allows the voltage clamping of different regions of the oocyte surface.

Animals↗
PubMed1997

A ryanodine-sensitive calcium store in ascidian eggs monitored by whole-cell patch-clamp recordings.

Using whole cell patch clamp recordings on unfertilized eggs of the ascidian Ciona intestinalis, we are able to detect ryanodine receptors within the oocytes. Our approach is based on measurements of the voltage-activated inward calcium currents. Two types of Ca2+ currents have been described on the oocyte membrane of Ciona: a low threshold slowly activating current, and a high threshold faster one. We show here that caffeine induces a decrease in the intensity of the Ca2+ currents, when applied either externally or internally from the mouth of a patch pipette. Caffeine application mimics fertilization which transiently decreases the high threshold Ca2+ current density during density during the first meiotic cycle. Ryanodine (> 1 nM) has an effect similar to caffeine. This partial decrease in Ca2+ current density elicited by caffeine or ryanodine is prevented by intracellular application of the calcium chelator BAPTA, then imputable to calcium release. In summary, the depolarization-induced Ca2+ current intensity allows monitoring of an intracellular calcium store which is sensitive to low concentrations of ryanodine in Ciona oocytes. Further identification of a ryanodine receptor was obtained by immunological staining with antibodies against mammalian skeletal muscle ryanodine receptor. Ryanodine receptors were asymmetrically localized in the cortex of Ciona eggs. We discuss the methodological relevance of our patch-clamp approach, in connection with the possible biological role of such a ryanodine receptor in the early stages of development.

Animals↗
PubMed2002

NEUROFIT: software for fitting Hodgkin-Huxley models to voltage-clamp data.

I introduce publicly available software for accurate fitting of Hodgkin-Huxley models to voltage-clamp data. I describe the model and non-linear fitting procedure employed by the software and compare its results with the usual method of fitting such models using potassium A-current data from a pyloric dilator cell of the lobster Panulirus interruptus and sodium current data from an electrocyte cell of the electric fish Sternopygus macrurus. The set of parameter values for the model determined by this software yield current traces that are substantially closer to the observed data than those determined from the usual fitting method. This improvement is due to the fact that the software fits all of the parameters simultaneously utilizing all of the data rather than fitting steady-state and time constant parameters disjointly using peak currents and portions of the rising and falling phases. I analyze the convergence properties of the software's fitting algorithm using simulated data showing that accurate parameter values are obtained for most of the parameters using any reasonable initial values. The software also incorporates a linear pre-estimation procedure to help in determining reasonable initial values for the full non-linear algorithm. I illustrate and discuss some of the inadequacies of voltage-clamp data.

Algorithms↗
PubMed1997

Rapid coating of glass-capillary microelectrodes for single-electrode voltage-clamp.

The single-electrode voltage-clamp technique requires sharp glass-capillary microelectrodes, whose electrical properties often limit the capabilities of the recording system. Here, we describe a rapid and simple way of coating fine microelectrodes with Dricote and Vaseline that improves their performance during voltage-clamp. The coating prevented clogging of the tips, improved the capacitance compensation of the electrodes, helped to seal the electrode tips into cell membranes and allowed visualization of the tips under saline solution. This new coating method led to greatly improved recordings and better characterization of the transduction and voltage-activated currents in an isolated preparation of spider mechanosensory neurons.

Animals↗
PubMed1997

A simple hardware model for the direct observation of voltage-clamp performance under realistic conditions.

A new hardware cell model for electrophysiological recording has been constructed which allows for the assessment of voltage clamp accuracy in different recording situations. Each compartment consists of a capacitor in parallel with a variable resistor and can be connected to other compartments by a variable axial resistance. The simulated membrane resistance can be changed extrinsically by a command voltage input which is optically coupled to the cell without any direct galvanic contact. Each compartment possesses a buffer amplifier which reads out the potential at the simulated membrane element, (e.g. 'somatic' or 'dendritic' potential). The model allows for the direct observation of typical situations and problems arising in electrophysiological experiments. We used the model to monitor deviations between the 'intracellular' and the command voltage, e.g. due to series resistance errors. We also used the model to simulate synaptic currents which were generated by triangular membrane conductance changes. The results demonstrate the strong influence of synaptic location and series resistance on voltage clamp fidelity. The cell model is a new and easy-to-handle tool for the observation of voltage control under realistic experimental conditions.

Animals↗
PubMed1998

A whole-cell clamp study of dendrodendritic synaptic activities in mitral cells of turtle olfactory bulb slices.

A procedure for preparing slices from the turtle olfactory bulb is described in this report. Individual layers of the bulb could be identified in the slices which enabled visual identification of cell types. Mitral cells retained extensive dendritic arborizations in slices of typical thickness, 300-400 microm. The presence of extensive dendritic processes was consistent with the difficulties we encountered in our attempt to achieve adequate space clamp. On the few occasions where an adequate space clamp of a mitral cell was achieved, calcium current exhibited a threshold of - 50 mV and reached its maximal level at - 10 mV. In all cases where calcium current was analysed (n=46), the current exhibited little inactivation. Depolarizing steps in 50% of the mitral cells triggered a burst of feedback synaptic activity after termination of the step. The intensity of feedback activity correlated closely with the amplitude of the depolarizing step, reaching its maximal level at - 10 mV and declining with further depolarization. The bell-shaped relationship between the feedback activity and mitral cell depolarization is consistent with the hypothesis that the feedback activity is mediated by reciprocal synapses on the mitral cell dendrite. This hypothesis is further supported by the inhibitory nature of the feedback synaptic activity: (i) the polarity of the feedback synaptic current could be inverted at the predicted chloride equilibrium potential, (ii) the feedback activity could be completely blocked by 10 microM bicuculline. The analysis of spontaneous synaptic activity showed that it was mostly inhibitory because its polarity could be reversed at the predicted chloride equilibrium potential. In some mitral cells, the frequency of spontaneous activity was noticeably increased when the holding potential was depolarized. This correlation could be attributed to the activation of dendrodendritic synapses. Results shown in this report demonstrate that dendrodendritic synapses are viable in turtle olfactory bulb slices. In addition, the suppression of feedback inhibition by large depolarizing steps of mitral cells suggests that the control of mitral cell dendritic potential is adequate to suppress calcium influx during large depolarizing steps.

Animals↗
PubMed1998

Dynamic clamp study of Ih modulation of burst firing and delta oscillations in thalamocortical neurons in vitro.

The dynamic clamp technique was used in thalamocortical neurons of the rat and cat dorsal lateral geniculate nucleus in vitro to investigate the effects of the hyperpolarization-activated cation current, Ih, and of its neuromodulation on burst firing and delta oscillations. Specific block of endogenous Ih using 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)pyridinium chloride (ZD7288) (300 microM) abolished the depolarizing "sag" response to negative current steps, markedly increased the latency and shortened the duration of the low-threshold Ca2+ potentials, and decreased the number of action potentials in the burst evoked by the low-threshold Ca2+ potential. Subsequent introduction of artificial Ih using the dynamic clamp re-instated the "sag" and all the original properties of the low-threshold Ca2+ potential. In the absence of ZD7288, introduction of artificial outward Ih with the intention of abolishing endogenous Ih removed the depolarizing "sag" and produced similar effects on the low-threshold Ca2+ potentials as those observed during the pharmacological block of Ih. Application of ZD7288 to thalamocortical neurons displaying delta oscillations led to a reduction in the voltage range of their existence or to a complete cessation of this behaviour. A subsequent introduction of artificial Ih re-enabled the generation of delta oscillations. In the presence of ZD7288, physiologically relevant positive shifts in the voltage-dependence of artificial Ih increased the amplitude and duration of the low-threshold Ca2+ potential and increased the likelihood of delta oscillations while negative shifts had opposite effects. These results highlight the important difference between the dependence of burst firing and oscillations on membrane potential and their dependence on the properties of Ih, and demonstrate that the modulation by Ih of low-threshold Ca2+ potentials and burst firing in thalamocortical neurons, as well as the ability of these neurons to generate delta oscillations, is more elaborate than previously described.

2-Amino-5-phosphonovalerate↗
PubMed1999

Effects of choline and other nicotinic agonists on the tectum of juvenile and adult Xenopus frogs: a patch-clamp study.

We have used anatomical methods and whole-cell patch-clamp recording to assess the distribution of nicotinic receptors in the tectum of Xenopus frogs and to measure effects of nicotinic ligands (carbachol, cytisine and nicotine) on glutamatergic spontaneous miniature excitatory postsynaptic currents. Our results confirm that retinotectal axons account for the majority of nicotinic receptors in the tectum and that nicotinic agonists exert presynaptic effects that increase the rate of transmitter release on to tectal cells. The nicotinic blockers mecamylamine and methyllycaconitine reduced responses to carbachol and cytisine. A small percentage of cells also showed postsynaptic responses. We have assessed whether there are developmental changes in the frequency of occurrence of spontaneous miniature excitatory postsynaptic currents. The first three months post-metamorphosis fall within the critical period for the dramatic plasticity displayed by binocular inputs during development in Xenopus. During this period, visual activity governs the formation of orderly maps relayed from the ipsilateral eye via the cholinergic projection from the nucleus isthmi to the tectum. In this study, we have found that critical-period tecta (two to 12 weeks postmetamorphosis) tend to have higher spontaneous activity than do older tecta (two to 69 weeks postmetamorphosis), and that nicotinic agonists increase that activity in both groups, with the result that the peak rates in response to nicotinic agonists are higher during the critical period than later. We also investigated the possible role of choline as an agonist of nicotinic receptors in the tectum. We have found that choline, as well as carbachol and cytisine, can cause a reversible increase in the rate of miniature excitatory postsynaptic currents. This result may help to explain how the isthmotectal projection, which accounts for the overwhelming majority of cholinergic input to the tectum, can exert effects on retinotectal terminals even though there are no morphologically identifiable synapses between the two populations. We have examined the morphology of cells filled with biocytin during the patch-clamp experiments, and we find that cells with dendrites in the stratum zonale, a layer with particularly dense input from the contralateral nucleus isthmi, have higher spontaneous activity than cells with dendrites that do not extend into that layer. Nicotinic agonists increased the activity recorded in both classes of cells. In addition, four pretectal cells were identified. Nicotinic agonists increased the rate of spontaneous activity recorded in that population. The results indicate that retinotectal transmission in the superior colliculus can be increased presynaptically by activity of the cholinergic projections of the nucleus isthmi. This modulation may be the basis for observations that blocking of cholinergic input disrupts the formation of topographic retinotectal projections. Moreover, the ability of choline to activate these receptors suggests that this metabolite of acetylcholine may permit paracrine activation of presynaptic receptors even though the tectum contains high acetylcholinesterase activity.

Aging↗
PubMed2001

Screening of ion channel receptor agonists using capillary electrophoresis-patch clamp detection with resensitized detector cells.

Efficient techniques for identifying endogenous and synthetic ligands of ion channels are important in understanding neuronal communication and for screening drug libraries. This paper describes a technique based on capillary electrophoresis (CE) separation coupled to patch-clamp (PC) detection where a pulsed-flow superfusion scheme was implemented for improved detection. The nicotinic acetylcholine receptor (nAChr) agonists acetylcholine, carbachol, and (-)-nicotine were fractionated and detected by patch-clamped pheochromcytoma detector cells. The high-conductance state of the nAChr during CE-PC detection was maintained and repetitively resensitized using pulsed-flow superfusion with agonist-free buffer. In this way, each agonist evoked an ensemble of peak currents that reflected the spatiotemporal distribution for the ligand at the cell surface. The technique takes advantage of the intrinsic high selectivity and sensitivity of membrane-expressed receptors and allowed for resolution and identification of closely migrating ligands. The method was employed for determination of acetylcholine content in cell lysates.

Acetylcholine↗
PubMed1997

Patch clamp detection in capillary electrophoresis.

We describe a capillary electrophoresis-patch clamp (CE-PC) analysis of biomolecules that activate ligand-gated ion channels. CE-PC offers a powerful means for identifying receptor ligands based on the combination of the characteristic receptor responses they evoke and their differential electrophoretic migration rates. Corner frequencies, membrane reversal potentials, and mean and unitary single-channel receptor responses were calculated from currents recorded with patch clamp detection. This information was then combined with the electrophoretic mobility of the receptor ligand, which is proportional to the charge-to-frictional-drag ratio of that species. We applied CE-PC to separate and detect the endogenous receptor agonists gamma-aminobutyrate and L-glutamate and the synthetic glutamate receptor agonists N-methyl-D-aspartate and kainic acid. We present dose-response data for electrophoretically separated kainic acid and discuss its implications for making the CE-PC detection system quantitative.

Animals↗
PubMed1998

Screening of receptor antagonists using agonist-activated patch clamp detection in chemical separations.

We present a capillary electrophoresis-patch clamp detection system optimized for screening of antagonists and inhibitors of ligand-gated ion channels. In this system, highly selective receptor agonists are delivered through the electrophoresis capillary to the cell surface where they continuously activate a receptor, resulting in increased steady-state transmembrane currents. Thus, receptor selection and biosensor functionality is simply achieved by selection of an appropriate agonist. The antagonists are fractionated in the same electrophoresis capillary and inhibit the agonist-evoked response, resulting in transiently decreased steady-state transmembrane currents. Specifically, a mixture containing 6-cyano-7-nitroquinoxaline-2,3-dione, that reversibly blocks alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate receptors, and 6,7-dichloro-3-hydroxy-2-quinoxaline-carboxylate, a broad-spectrum glutamate receptor antagonist, were separated and detected by kainate-activated patch-clamped interneurons freshly dissociated from rat brain olfactory bulb. In addition, Mg2+ that reversibly blocks the N-methyl-D-aspartate receptor in a voltage-dependent way was detected using the same cell detector system when activated by N-methyl-D-aspartate and the co-agonist glycine. The presented method offers new possibilities for drug screening and for identifying endogenous receptor antagonists and to determine their mode of action on any ionotropic receptor system of interest.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2006

The glucose clamp reveals an association between adiponectin gene polymorphisms and insulin sensitivity in obese subjects.

Results concerning the association of adiponectin gene polymorphisms (single-nucleotide polymorphisms, SNPs) with obesity, type 2 diabetes (T2DM), metabolic disorders and insulin resistance have not lead to definite conclusions. The aim of our study was to investigate a possible association between the -11391G>A and -11377C>G SNPs of adiponectin gene and measure of insulin sensitivity evaluated by the hyperinsulinemic-euglycemic clamp in a group of 'uncomplicated' obese subjects (with no associated comorbidities) (n=99, mean age 35 years) with a history of obesity lasting at least 10 years. The study of uncomplicated obese subjects, free of possible confounding factors that could interfere with insulin sensitivity, such as pharmacological treatment, provides a good model to assess insulin sensitivity per se. We observed that subjects homozygous for the G allele at locus -11391 had lower M (mg/kg min)/fat-free mass (FFM) index and adiponectin levels compared to subjects with GA+AA genotypes (P=0.002 and P=0.03, respectively) and subjects carrying the -11377G variant had lower M (mg/kg min)/FFM index and adiponectin levels compared to noncarriers (P=0.003 and P=0.03, respectively). Our results imply that the two promoter SNPs, -11391G>A and -11377C>G, of the adiponectin gene are associated with a reduced insulin sensitivity evaluated by hyperinsulinemic-euglycemic clamp in obese subjects.

Adiponectin↗
PubMed1994

Assessment of insulin sensitivity in man: a comparison of minimal model- and euglycaemic clamp-derived measures in health and heart failure.

1. Simplified protocols for the measurement of insulin resistance will facilitate studies of this potentially important variable. 2. Using the euglycaemic clamp as the reference technique, we have assessed the validity of the insulin sensitivity index (inversely related to insulin resistance) obtained using a high-dose (500 mg/kg), unmodified intravenous glucose tolerance test with a 16 point sampling schedule and analysis using the minimal model of glucose disappearance. The two methods were compared in 10 clinically normal subjects and five patients with severe heart failure secondary to coronary heart disease. 3. The insulin sensitivity index of the minimal model was compared with four clamp-derived measures. Correlation coefficients of 0.72-0.92 (P < 0.01-P < 0.001) were obtained between the two methods over a wide range of insulin sensitivity [model values 1.03-14.63 min-1/(pmol/l) x 10(-5)]. Patients with heart failure had the lowest measures of insulin sensitivity. 4. The high-dose, unmodified intravenous glucose tolerance test with minimal model analysis is a straightforward and economical clinical procedure and provides a valid measure of insulin sensitivity, in health and disease.

Adult↗
PubMed1998

Patch-clamp analysis of the mechanism of PACAP-induced excitation in rat supraoptic neurones.

In neurosecretory cells of the supraoptic nucleus (SON) of rats, pituitary adenylate cyclase activating polypeptide (PACAP) causes an increase in [Ca2+]i, and stimulates somatodendritic vasopressin (VP) release. In this report, to elucidate the ionic mechanism of the action of PACAP, membrane potentials and ionic currents were measured from SON neurones in slice preparations or from dissociated SON neurones. In the current clamp mode, PACAP depolarized membrane potentials of both phasic and non-phasic neurones and increased the firing rate. Moreover, simultaneous measurements of membrane potentials and [Ca2+]i revealed that the membrane depolarization correlated well with increases in [Ca2+]i. In the voltage-clamp mode, PACAP induced inward currents at a holding potential of -70 or -80 mV in a dose-dependent manner and the time course of the currents was similar to that of the PACAP-induced membrane depolarization. The averaged reversal potential of the PACAP-induced currents obtained from dissociated SON neurones was -33 mV, which was close to the reversal potential of non-selective cation currents in SON neurones. The currents were rapidly and reversibly inhibited by a cation-channel blocker, gadolinium. Analysis of synaptic inputs into SON neurones in slice preparations revealed that PACAP had little or no effects on the frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results suggest that pituitary adenylate cyclase activating polypeptide (PACAP) activates PACAP receptors in the postsynaptic membrane of the supraoptic nucleus (SON) neurones, and that the activation of PACAP receptors leads to opening of non-selective cation channels, depolarization of the membrane potential, and increase in the firing rate in SON neurones. Such mechanisms may account for the PACAP-induced increase in [Ca2+]i and vasopressin (VP) release observed in SON neurones.

Adenylyl Cyclases↗
PubMed2003

Isolation of AtSUC2 promoter-GFP-marked companion cells for patch-clamp studies and expression profiling.

K+ channels control K+ homeostasis and the membrane potential in the sieve element/companion cell complexes. K+ channels from Arabidopsis phloem cells expressing green fluorescent protein (GFP) under the control of the AtSUC2 promoter were analysed using the patch-clamp technique and quantitative RT-PCR. Single green fluorescent protoplasts were selected after being isolated enzymatically from vascular strands of rosette leaves. Companion cell protoplasts, which could be recognized by their nucleus, vacuole and chloroplasts, and by their expression of the phloem-specific marker genes SUC2 and AHA3, formed the basis for a cell-specific cDNA library and expressed sequence tag (EST) collection. Although we used primers for all members of the Shaker K+ channel family, we identified only AKT2, KAT1 and KCO6 transcripts. In addition, we also detected transcripts for AtPP2CA, a protein phosphatase, that interacts with AKT2/3. In line with the presence of the K+ channel transcripts, patch-clamp experiments identified distinct K+ channel types. Time-dependent inward rectifying K+ currents were activated upon hyperpolarization and were characterized by a pronounced Ca2+-sensitivity and inhibition by protons. Whole-cell inward currents were carried by single K+-selective channels with a unitary conductance of approximately 4 pS. Outward rectifying K+ channels (approximately 19 pS), with sigmoidal activation kinetics, were elicited upon depolarization. These two dominant phloem K+ channel types provide a versatile mechanism to mediate K+ fluxes required for phloem action and potassium cycling.

Arabidopsis↗
PubMed2003

An insulin-resistant hypertriglyceridaemic normotensive obese dog model: assessment of insulin resistance by the euglycaemic hyperinsulinaemic clamp in combination with the stable isotope technique.

Many studies have shown that in humans insulin resistance (IR) is associated with obesity and hypertriglyceridaemia. The aim of our study was to develop slowly dietary-induced obesity in dogs through long-term overfeeding of a high-fat diet, and to characterize this IR, hypertriglyceridaemic and normotensive model. Insulin resistance was assessed by the euglycaemic hyperinsulinaemic clamp technique. The contribution of hepatic glucose production during the clamp was evaluated using a constant stable-isotope-labelled glucose infusion. Overfeeding a high-fat diet for 7 months was associated with a 43+/-5% body weight increase. Insulin resistance was characterized by hyperinsulinaemia in the unfed state (10+/-1 vs. 24+/-1 microU/ml, in healthy and obese dogs, respectively, p<0.02) and by a reduction of the insulin-mediated glucose uptake (28+/-3 vs. 16+/-1 mg/kg/min, p<0.02). Hepatic glucose production suppression under insulin infusion allowed to conclude that this reduced glucose uptake resulted from a decrease of insulin sensitivity in obese dogs. Furthermore, animals remained normotensive and exhibited a marked hypertriglyceridaemia (0.26+/-0.04 vs. 0.76+/-0.15 mmol/l, in healthy and obese dogs, respectively, p<0.02). Because hypertriglyceridaemia is the most common lipid abnormality in insulin-resistant humans, this dog with slowly induced obesity may constitute a good model to study the consequences of IR in lipid metabolism independently of vascular changes.

Animals↗