Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CLAMPS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed1999

Influence of non-steady state during isoglycemic hyperinsulinemic clamp in hypertension. A LIFE substudy.

We wanted to investigate whether time to steady state was reached within 2 h of insulin infusion during isoglycemic hyperinsulinemic clamp, comparing the glucose uptake index (M/IG) with Bergman's insulin sensitivity index (Sip). We performed a 2-h oral glucose tolerance test and a 3-h isoglycemic hyperinsulinemic clamp in 26 young, healthy subjects and 43 elderly patients with unmedicated essential hypertension and left ventricular hypertrophy. The 3-h Sip correlated strongly with the 2-h M/IG in the patients (r = 0.88, p < 0.001) as well as in the healthy subjects (r = 0.96, p < 0.001) with relatively narrow limits of agreement in the patients. However, during the third hour of insulin infusion, M/IG (10.0 vs 12.21(2) x kg(-1) x min(-1) x mmol(-1), p < 0.001) as well as Sip (7.1 vs 9.41(2) x kg(-1) x min(-1) x mmol(-1), p < 0.001) increased significantly in the patients, but not in the healthy subjects. Because the 2-h M/IG correlated strongly with the 3-h Sip with relatively narrow limits of agreement, it is a good measure of insulin sensitivity. However, a 2-h clamp results in lower insulin sensitivity values in elderly, hypertensive patients due to the fact that steady state is not reached, demonstrating a higher prevalence of insulin resistance in such a population.

Adult↗
PubMed1959

Voltage clamp behavior of iron-nitric acid system as compared with that of nerve membrane.

The current-voltage relation for the surface layer of an iron wire immersed in nitric acid was investigated by the voltage clamp technique. Comparing the phase of nitric acid to the axoplasm and the metallic phase to the external fluid medium for the nerve fiber, a striking analogy was found between the voltage clamp behavior of the iron-nitric acid system and that of the nerve membrane. The current voltage curve was found to consist of three parts: (a) a straight line representing the behavior of the resting (passive) membrane, (b) a straight line representing the fully excited (active) state, and (c) an intermediate zone connecting (a) and (b). It was shown that in the intermediate zone, the surface of iron consisted of a fully active patch (or patches) surrounded by a remaining resting area. The phenomenon corresponding to "repetitive firing of responses under voltage clamp" in the nerve membrane was demonstrated in the intermediate zone. The behavior of the cobalt electrode system was also investigated by the same technique. An attempt was made to interpret the phenomenon of initiation and abolition of an active potential on the basis of the thermodynamics of irreversible processes.

Iron↗
PubMed2001

Information technology and home glucose clamping.

Persons with diabetes are responsible for the day-to-day control of their glycemia. To assist patients in discharging this responsibility and help them achieve and sustain improvements in self-blood glucose control, we developed information technology capable of executing algorithms for "clamping glucose" at home. Algorithms for laboratory glucose clamping were translated and adapted for use by patients. The procedures were supported by a central computer and registry. Interaction with the algorithms from home required the patient to handle only a touch-tone telephone, which accessed voice response hardware in the central computer. Patients reported self-measured blood glucose levels or hypoglycemia symptoms together with dietary changes, planned exercise, stress, illness or other lifestyle events. In response, they received self-management instructions and dosing decision support. Metabolic end points were measured. System beta testing in active patients was for 1 year. Patients (n = 142) used the algorithms for their daily self-management, accumulating 1,651 patient-months of follow-up. Almost 100,000 telephone calls were received. Patients benefited. Prevalence of diabetes related crises (hyperglycemia > 400 mg/dL, hypoglycemia < 50 mg/dL or symptoms without measurement) fell approximately twofold (p < 0.05) and glycated hemoglobin levels fell 1.3% (p < 0.001), while body weight was stable. Providers benefited from the timely receipt of standardized reports to monitor the progress of their patients. Earlier intervention was possible. Information technology facilitated home glucose clamping whereby patients with diabetes received timely assistance, advice and decision support for crucial self-control of blood glucose levels. This empowered patients to achieve independence and improve diabetes self-management.

Algorithms↗
PubMed2003

A benchmark study with sealchip planar patch-clamp technology.

Although conventional patch-clamp methods provide high information content, they are labor-intensive and suffer from low throughput and high overall cost. Several approaches for achieving high throughput electrophysiology are under development, among which microchip-based patch-clamp systems uniquely achieve a higher degree of miniaturization, faster perfusion and mixing, and lower reagent cost without losing information content. The goal of this study was to establish a benchmark for our biochip technology with 52 chips tested sequentially. We demonstrate that our microfabrication and processing technology is sufficiently mature to produce a consistent hole size. We further demonstrate high-quality planar whole-cell patch clamping with >75% overall success rate at achieving gigaohm seals, followed by stable whole-cell access lasting at least 15 min with access resistance (Ra) below 15 MOmega and membrane resistance (Rm) above 200 MOmega. These biochips are ideally suited for high throughput compound screening for ion channel targets.

Animals↗
PubMed2003

Characterization of potassium channel modulators with QPatch automated patch-clamp technology: system characteristics and performance.

Planar silicon chips with 1-2-microm etched holes (average resistance: 2.04 +/- 0.02 MOmega in physiological buffer, n = 274) have been developed for patch-clamp recordings of whole-cell currents from cells in suspension. An automated 16-channel parallel screening system, QPatch 16, has been developed using this technology. A single-channel prototype of the QPatch system was used for validation of the patch-clamp chip technology. We present here data on the quality of patch-clamp recordings and from actual drug screening studies of human potassium channels expressed in cultured cell lines. Using Chinese hamster ovary (CHO) and human embryonic kidney cells (HEK), gigaseals of 4.1 +/- 0.4 GOmega (n = 146) and high-quality whole-cell current recordings were obtained from hERG and KCNQ4 potassium channels. Success rates for gigaseal recordings varied from 40 to 95%, and 67% of the whole-cell configurations lasted for >20 min. Cells were maintained in suspension up to 4 h in a cell storage facility that is integrated in the QPatch 16. No decline in patchability was observed during this time course. A series of screens was conducted with known inhibitors of the hERG and KCNQ4 potassium channels. Dose-response relationship characterizations of verapamil and rBeKm-1 blockage of hERG currents provided IC(50) values similar to values reported in the literature.

Animals↗
PubMed2006

Transient and steady-state euglycemic clamp validation of a model for glycemic control and insulin sensitivity testing.

BACKGROUND: There is an urgent need for a simple and accurate measure of insulin sensitivity to diagnose insulin resistance in the general population and quantify changes due to clinical intervention. A new physiological control model of glucose and insulin metabolism is validated with the euglycemic-hyperinsulinemic clamp during steady and transient states. METHODS: The data consist of n = 60 (15 lean, 15 overweight, 15 obese, and 15 morbidly obese) euglycemic-hyperinsulinemic clamp trials performed on normoglycemic insulin-resistant individuals. The glucose and insulin model is fitted using an integral-based method. Correlations between clamp-derived insulin sensitivity index (ISI) and the model's insulin sensitivity parameter (SI) are obtained during steady and transient states. Results are compared with log-homeostasis model assessment (HOMA), a widely used fasting surrogate for insulin sensitivity. RESULTS: Correlation between model-based insulin sensitivity, SI, and ISIG (ISI normalized by steady-state glucose) is r = 0.99 (n = 60) at steady state and r = 0.97 at transient state, respectively. Correlations did not significantly change across subgroups, with narrow 95% confidence intervals. Log-HOMA correlations are r=-0.72 to SI and r=-0.71 to ISIG for the overall population but are significantly lower in the subgroups, with wide 95% confidence intervals. CONCLUSIONS: The model-based insulin sensitivity parameter, SI, highly correlates to ISIG in all subgroups, even when only considering a transient state. The high correlation of SI offers the potential for a short, simple yet highly correlated, model-based assessment of insulin sensitivity that is not currently available.

Adult↗
PubMed2005

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp.

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis. METHODS: After 60 min of stabilization, 38 anesthetized and mechanically ventilated pigs (weight, 35-40 kg) were divided (by randomization performed before the experiment) into four groups and were then studied for 570 min. Group 1 received no intervention. Group 2 received a HEC (5 mm p-glucose, insulin infusion rate of 0.6 mU . kg (-1). min(-1)) for 570 min. Group 3 received a lipopolysaccharide infusion for 180 min. Group 4 was given a combination of a HEC and a lipopolysaccharide infusion. After the 570-min study period, the pigs were killed, and tissue was sampled from the spleen and frozen. In four sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number of apoptotic B and T lymphocytes was then compared using two-way analysis of variance, and the interaction between endotoxemia and the clamp (hyperinsulinemia and euglycemia) was investigated. RESULTS: Endotoxemia induced apoptosis of B (P < 0.001) and T lymphocytes (P = 0.016) in the spleen, and this effect was independent of the clamp. The ratios of apoptotic cells in the spleen tissue of pigs with and without endotoxemia were 2.4 (confidence interval, 1.7-3.4) and 1.6 (confidence interval, 1.1-2.2) for B and T lymphocytes, respectively. Independent of endotoxin infusion, HEC increased the number of apoptotic lymphocytes (P = 0.029 and P = 0.038 for B and T lymphocytes, respectively). The ratios of the number of apoptotic spleen cells in pigs treated and not treated with HEC were 1.5 (confidence interval, 1.0-2.1) and 1.5 (confidence interval, 1.0-2.1) for B and T lymphocytes, respectively. CONCLUSION: In this porcine model, both endotoxemia and a HEC increased the number of apoptotic B and T lymphocytes in the spleen. Contrary to our hypothesis, lymphocyte apoptosis during acute endotoxemia was augmented by a HEC.

Algorithms↗
PubMed1999

Artifactual voltage response recorded from hair cells with patch-clamp amplifiers.

Patch-clamp amplifiers (PCAs) are commonly used to characterize voltage- and current-clamp responses in the same cell. However, the cell membrane voltage response can be severely distorted by PCAs working in the current-clamp mode. Here we compare the voltage response of pigeon semicircular canal hair cells in situ, recorded with two different PCAs, and with a classic microelectrode bridge amplifier (BA). We found that the voltage response of hair cells recorded with PCAs differed significantly from that recorded with the BA. The true hair cell membrane voltage response to positive current steps was characterized by a strongly damped oscillation, whose frequency and duration depended on hair cell location in the sensory crista ampullaris.

Animals↗
PubMed1997

Cardiac 18F-FDG-SPET studies in patients with non-insulin-dependent diabetes mellitus during hyperinsulinaemic euglycaemic clamping.

Identification of viable myocardium is possible with 18F-fluorodeoxyglucose (FDG) and positron emission tomography (PET). More recently, the feasibility of cardiac FDG imaging with single photon emission tomography (SPET) has been reported. In patients with diabetes mellitus, poor image quality is frequently obtained with FDG-PET, due to relative or absolute insulin deficiency and peripheral insulin resistance. To improve image quality of the FDG-PET studies, the hyperinsulinaemic glucose clamp has been proposed. We assessed the image quality of cardiac FDG-SPET studies in 10 patients with non-insulin-dependent diabetes mellitus (NIDDM) and compared the results with those obtained in 10 patients without NIDDM. All FDG studies were performed during hyperinsulinaemic glucose clamping. Image quality was expressed as myocardial to blood pool activity (M/B) ratios. Residual viability was assessed in dysfunctional myocardium. The M/B ratios were comparable between patients with and without NIDDM (2.67 +/- 0.8 vs 2.50 +/- 0.7, N.S.). Residual viability was detected in 51% of the dysfunctional segments of the patients with NIDDM and in 49% of the segments of the patients without NIDDM. In the small subset of patients (n = 10) undergoing revascularization, 19 of 20 (95%) segments that had improved wall motion were viable on FDG-SPET. In contrast, 27 of 36 (75%) segments that did not improve were necrotic on FDG-SPET. Thus FDG-SPET during hyperinsulinaemic glucose clamping provides adequate image quality in patients with NIDDM compared with patients without NIDDM, and can be used in the detection of viable myocardium.

Aged↗
PubMed1999

Responsiveness of rat substantia gelatinosa neurones to mechanical but not thermal stimuli revealed by in vivo patch-clamp recording.

1. Synaptic responses of 46 substantia gelatinosa (SG) neurones in the spinal dorsal horn to cutaneous mechanical and/or thermal stimuli were investigated in an in vivo rat preparation with whole-cell patch-clamp recordings. The clamped neurones were identified as being in the SG based on either their morphological features by intrasomatic injection of biocytin or the depth of the neurones from the surface of the spinal cord. 2. In all SG neurones examined where spontaneous EPSCs occurred, pinch (noxious) and air (innocuous) stimuli applied to the ipsilateral hindlimb elicited a barrage of EPSCs (some of which initiated an action potential under current-clamp conditions), which subsided just after cessation of the stimuli without any residual slow current (or after-discharge). The spontaneous and evoked EPSCs were reversibly abolished by a non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, CNQX (20 microM). 3. Noxious (>= 45 C) or innocuous (<= 40 C) thermal stimuli did not elicit any synaptic responses in all 18 SG neurones tested which were sensitive to mechanical stimuli. Noxious cold stimulation (<= 10 C) also failed to produce any responses (n = 6). 4. It is concluded that both noxious and innocuous mechanical information to SG neurones are transmitted primarily by activation of non-NMDA receptors, probably without any involvement of slow synaptic transmission, and that thermal information is conveyed to areas of the dorsal horn other than SG.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Presynaptic calcium currents at voltage-clamped excitor and inhibitor nerve terminals of crayfish.

1. A two-electrode voltage clamp was used to record calcium currents from the excitatory and inhibitory nerve terminals that innervate the crayfish (Procambarus spp.) opener muscle. Other voltage-dependent currents were blocked with tetrodotoxin, 3,4-diaminopyridine, 4-aminopyridine and tetraethylammonium. 2. The presynaptic calcium current at both excitatory and inhibitory synapses was blocked by cadmium and omega-agatoxin IVA but was not affected by omega-conotoxin GVIA, omega-conotoxin MVIIC or nifedipine, suggesting that the calcium currents flow through P-type calcium channels. 3. Current-voltage (I-V) relations at both excitatory and inhibitory synapses are similar, with current activation near -40 mV, peak current near -10 mV and current reversal at membrane potentials greater than +25 mV. I-V relations were scaled along the current axis by partial calcium current blockade with cobalt, suggesting that series resistance and space-clamp errors were small. 4. A subset of terminals on one muscle fibre was locally superfused with a physiological saline containing barium; the rest of the preparation was superfused with a physiological saline containing calcium channel antagonists. Under such conditions the characteristics of the I-V relation were very similar to the I-V relations recorded when the entire preparation was bathed in physiological levels of calcium, suggesting that the space clamp was adequate. 5. Calcium channel activation, as determined from tail current analyses, was similar when the entire preparation was bathed in physiological levels of calcium or if terminals on one muscle fibre were locally superfused with barium. 6. During a 30 ms depolarization, calcium currents inactivated to a greater extent in inhibitory than in excitatory terminals. The inactivation was of small magnitude (< 20%) and was eliminated by intracellular injection of the calcium chelator BAPTA, suggesting that the inactivation was calcium dependent. 7. These data show that biophysical and pharmacological properties of calcium currents at crayfish neuromuscular junctions resemble those found at stellate synapses in squid.

Animals↗
PubMed2003

Patch-clamp analysis in canine cardiac Purkinje cells of a novel sodium component in the pacemaker range.

A putative Na+ component playing a role in the initiation and maintenance of spontaneous discharge in Purkinje fibres was studied by means of the whole-cell patch-clamp technique in canine cardiac single Purkinje cells. In 4 mM [K+]o, during depolarising clamp steps, a slowly inactivating current appeared at approximately -58 mV, negative to the threshold for the fast Na+ current (INa; approximately -50 mV). During depolarising ramps, the current underwent inward rectification with a negative slope region that began at approximately -60 mV. The current underlying the negative slope increased during faster ramps, decreased as a function of time when the initial depolarising ramp was over, decreased during depolarisations positive to approximately -35 mV and was much larger than the current during the symmetrical repolarising ramp. Increasing biphasic ('oscillatory') voltage ramps required much smaller currents at a holding potential (Vh) of -60 mV than at -80 mV and were associated with a marked decrease in slope conductance. At Vh -50/-40 mV, the oscillatory ramp currents and superimposed pulse currents reversed direction. The negative slope in the I-V relation as well as the change in current direction at -50/-40 mV were markedly reduced by tetrodotoxin (15 microM) and lidocaine (lignocaine, 100 microM) and therefore are due to a slowly inactivating Na+ current, labelled here INa3. Lower [K+]o (2.7 mM) reduced the steady state slope conductance as well as the current in the diastolic range, and increased as well as shifted INa3 in a negative direction. High [K+]o had the opposite effects. Cs+ (2 mM) and Ba2+ (2 mM) reduced the initial current during depolarising ramps but not INa3. In current-clamp mode, current-induced voltage oscillations elicited action potentials through a gradual transition between diastolic depolarisation and upstroke, consistent with the activation of INa3. Thus, the initiation and maintenance of spontaneous discharge in Purkinje strands appear to involve a voltage- and K+-dependent decrease in K+ conductance as well as the activation of a voltage- and time-dependent inward Na+ current (INa3) with slow inactivation kinetics.

Algorithms↗
PubMed2004

How shunting inhibition affects the discharge of lumbar motoneurones: a dynamic clamp study in anaesthetized cats.

In the present work, dynamic clamp was used to inject a current that mimicked tonic synaptic activity in the soma of cat lumbar motoneurones with a microelectrode. The reversal potential of this current could be set at the resting potential so as to prevent membrane depolarization or hyperpolarization. The only effect of the dynamic clamp was then to elicit a constant and calibrated increase of the motoneurone input conductance. The effect of the resulting shunt was investigated on repetitive discharges elicited by current pulses. Shunting inhibition reduced very substantially the firing frequency in the primary range without changing the slope of the current-frequency curves. The shift of the I-f curve was proportional to the conductance increase imposed by the dynamic clamp and depended on an intrinsic property of the motoneurone that we called the shunt potential. The shunt potential ranged between 11 and 37 mV above the resting potential, indicating that the sensitivity of motoneurones to shunting inhibition was quite variable. The shunt potential was always near or above the action potential voltage threshold. A theoretical model allowed us to interpret these experimental results. The shunt potential was shown to be a weighted time average of membrane voltage. The weighting factor is the phase response function of the neurone that peaks at the end of the interspike interval. The shunt potential indicates whether mixed synaptic inputs have an excitatory or inhibitory effect on the ongoing discharge of the motoneurone.

Action Potentials↗
PubMed2005

Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique.

Long-QT3 syndrome (LQT3) is linked to cardiac sodium channel gene (SCN5A) mutations. In this study, we used the 'dynamic action potential clamp' (dAPC) technique to effectively replace the native sodium current (I(Na)) of the Priebe-Beuckelmann human ventricular cell model with wild-type (WT) or mutant I(Na) generated in a human embryonic kidney (HEK)-293 cell that is voltage clamped by the free-running action potential of the ventricular cell. We recorded I(Na) from HEK cells expressing either WT or LQT3-associated Y1795C or A1330P SCN5A at 35 degrees C, and let this current generate and shape the action potential (AP) of subepicardial, mid-myocardial and subendocardial model cells. The HEK cell's endogenous background current was completely removed by a real-time digital subtraction procedure. With WT I(Na), AP duration (APD) was longer than with the original Priebe-Beuckelmann model I(Na), due to a late I(Na) component of approximately 30 pA that could not be revealed with conventional voltage-clamp protocols. With mutant I(Na), this late component was larger ( approximately 100 pA), producing a marked increase in APD ( approximately 70-80 ms at 1 Hz for the subepicardial model cell). The late I(Na) magnitude showed reverse frequency dependence, resulting in a significantly steeper APD-frequency relation in the mutant case. AP prolongation was more pronounced for the mid-myocardial cell type, resulting in increased APD dispersion for each of the mutants. For both mutants, a 2 s pause following rapid (2 Hz) pacing resulted in distorted AP morphology and beat-to-beat fluctuations of I(Na). Our dAPC data directly demonstrate the arrhythmogenic nature of LQT3-associated SCN5A mutations.

Action Potentials↗
PubMed1995

Chorda tympani taste response of rat to hydrochloric acid subject to voltage-clamped lingual receptive field.

The chorda tympani nerve response of the rat to HCl was obtained with the lingual receptive field under voltage clamp. Unlike NaCl responses, HCl responses were not affected by inside positive voltage perturbations. However, HCl responses under negative voltage clamp were suppressed in contrast to NaCl responses, which were enhanced. Unlike NaCl responses, HCl responses were amiloride insensitive. HCl rinsing from the tongue produced a large off-response. At zero current clamp the off-response coincided with an anomalous increased positive potential. The paracellular resistance was also higher for HCl relative to the same concentration of NaCl. This is evidence that H+ binds to the normally fixed anionic sites of the paracellular pathway rendering it anion selective. It is postulated that release of bound H+ from surface buffer sites is responsible for the second burst of neural activity upon rising HCl. Acids stimulate primarily through the paracellular pathway, which also furnishes buffering sites that regulate H+ concentration, thereby protecting the sensory apparatus from hyperacidic conditions.

Amiloride↗
PubMed2000

LabPatch, an acquisition and analysis program for patch-clamp electrophysiology.

An acquisition and analysis program, "LabPatch," has been developed for use in patch-clamp research. LabPatch controls any patch-clamp amplifier, acquires and records data, runs voltage protocols, plots and analyzes data, and connects to spreadsheet and database programs. Controls within LabPatch are grouped by function on one screen, much like an oscilloscope front panel. The software is mouse driven, so that the user need only point and click. Finally, the ability to copy data to other programs running in Windows 95/98, and the ability to keep track of experiments using a database, make LabPatch extremely versatile. The system requirements include Windows 95/98, at least a 100-MHz processor and 16 MB RAM, a data acquisition card, digital-to-analog converter, and a patch-clamp amplifier. LabPatch is available free of charge at http://www.fhs.mcmaster.ca/huizinga/.

Computer Graphics↗
PubMed1997

Interaction of exercise, insulin, and hypoglycemia studied using euglycemic and hypoglycemic insulin clamps.

Hyperinsulinemic euglycemic and hypoglycemic clamps were used to study the interaction of exercise, insulin, and hypoglycemia at rest and during exercise in the dog. Sampling (artery and portal, hepatic, and iliac veins) and infusion (vena cava) catheters and a flow probe (external iliac artery) were implanted surgically >16 days before study. After an 18-h fast and an 80-min tracer equilibration period, dogs were studied in the basal state (t = -40 to 0 min) and during a moderate treadmill exercise (t = 0-150 min) period or an equivalent duration sedentary period. Insulin was infused at 1 mU x kg(-1) x min(-1) from t = 0-150 min. In one group of sedentary (n = 7) and one group of exercised (n = 6) dogs, glucose was clamped at basal during the insulin infusion. In another group of sedentary (n = 6) and another group of exercised (n = 6) dogs, arterial glucose was clamped at hypoglycemic levels (approximately 65 mg/dl) during the insulin infusion. Arteriovenous difference and isotopic ([3-(3)H]glucose, [U-(14)C]glucose) techniques were used to assess glucose metabolism. Insulin levels were approximately 40 microU/ml in all groups. Data show that 1) counterregulatory hormone (glucagon, catecholamines, and cortisol) responses to exercise and hypoglycemia combined are synergistically higher than the response to either stimulus alone; 2) exercise-induced increases in insulin action are negated during hypoglycemia by the counterregulatory response; 3) decreased need for exogenous glucose during hypoglycemic compared with euglycemic exercise is due to stimulation of endogenous glucose production, which accounts for approximately 30% of the decrease, and reduction of glucose utilization, which accounts for approximately 70%; and 4) insulin-stimulated nonoxidative glucose metabolism is unaffected by exercise or hypoglycemia, whereas insulin-stimulated oxidative glucose metabolism is selectively increased by exercise and decreased by hypoglycemia. In conclusion, the marked rise in insulin action during exercise is matched, under insulin-induced hypoglycemic conditions, by an equally profound increase in counterregulation. The effectiveness of the potent insulin counterregulatory response may be important in decreasing the magnitude and frequency of exercise-induced hypoglycemia.

Animals↗
PubMed1997

Insulin-stimulated amino acid utilization during glucose and amino acid clamps decreases with development.

Neonatal animals utilize their dietary amino acids for protein accretion with high efficiency, and this efficiency declines during early life. The factors responsible for this developmental change are unknown. Our objectives were to determine whether amino acid (AA) utilization is stimulated by insulin in the neonate and whether this response changes during the suckling period. Two hyperinsulinemic-euglycemic clamp infusion studies, using 10-2,000 ng insulin.kg-0.66.min-1, were performed in 7- and 26-day-old pigs. In study I, no AA were provided during the infusion, and the resultant decline in plasma AA levels was defined. In study II, plasma AA were clamped at near-fasting levels, and whole body utilization of exogenous AA was determined by measuring the rate of infusion of an AA mixture necessary to maintain basal plasma lysine concentrations. In study I, the half-maximal effective dose (ED50) for the fall in AA concentrations with increasing plasma insulin concentration was lower in 7- than in 26-day-old pigs, and the nadir in AA concentration was achieved by only 20 microU/ml insulin. In study II, the utilization of exogenous AA during hyperinsulinemic-euglycemic AA clamps exhibited a higher maximum response (Rmax) (49 vs. 26 mumol AAtotal.min-1.kg-1) and a lower ED50 (18 vs. 45 microU insulin/ml) in 7- than in 26-day-old pigs. Plasma urea nitrogen concentrations did not rise with increasing insulin and AA infusion rates. These results indicate that insulin stimulates the utilization of exogenous AA in neonatal pigs and that both the insulin sensitivity and responsiveness of AA utilization decline over the suckling period. The infused AA were likely utilized for protein accretion.

Aging↗