Search PubMed⌕ Search

Biomedical subjects

C Cobelli

Publications and source records attributed to C Cobelli.

At least 91 records · Page 5Linked to original sources
PubMed1996

Roles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM.

Insulin resistance for glucose metabolism in skeletal muscle is a key feature in NIDDM. The quantitative role of the cellular effectors of glucose metabolism in determining this insulin resistance is still imperfectly known. We assessed transmembrane glucose transport and intracellular glucose phosphorylation in vivo in skeletal muscle in nonobese NIDDM patients. We performed euglycemic insulin clamp studies in combination with the forearm balance technique (brachial artery and deep forearm vein catheterization) in five nonobese NIDDM patients and seven age- and weight-matched control subjects (study 1). D-Mannitol (a nontransportable molecule), 3-O-[14C]methyl-D-glucose (transportable, but not metabolizable) and D[3-3H]glucose (transportable and metabolizable) were simultaneously injected into the brachial artery, and the washout curves were measured in the deep venous effluent blood. In vivo rates of transmembrane transport and intracellular phosphorylation of D-glucose in forearm muscle were determined by analyzing the washout curves with the aid of a multicompartmental model of glucose kinetics in forearm tissues. At similar steady-state concentrations of plasma insulin (approximately 500 pmol/l) and glucose (approximately 5.0 mmol/l), the rates of transmembrane influx (34.3 +/- 9.1 vs. 58.5 +/- 6.5 micromol x min(-1) x kg(-1), P < 0.05) and intracellular phosphorylation (5.4 +/- 1.6 vs. 38.8 +/- 5.1 micromol x min(-1) x kg(-1), P < 0.01) in skeletal muscle were markedly lower in the NIDDM patients than in the control subjects. In the NIDDM patients (study 2), the insulin clamp was repeated at hyperglycemia, (approximately 13 mmol/l) trying to match the rates of transmembrane glucose influx measured during the clamp in the controls. The rate of transmembrane glucose influx (62 +/- 15 micromol x min(-1) x kg(-1)) in the NIDDM patients was similar to the control subjects, but the rate of intracellular glucose phosphorylation (16.6 +/- 7.5 micromol x min(-1) x kg(-1)), although threefold higher than in the patients during study 1 (P < 0.05), was still approximately 60% lower than in the control subjects (P < 0.05). These data suggest that when assessed in vivo, both transmembrane transport and intracellular phosphorylation of glucose are refractory to insulin action and add to each other in determining insulin resistance in skeletal muscle of NIDDM patients. It will be of interest to compare the present results with the in vivo quantitation of the initial rate of muscle glucose transport when methodology to perform this measurement becomes available.

3-O-Methylglucose↗
PubMed1996

Reconstruction of insulin secretion rate by deconvolution: domain of validity of a monoexponential C-peptide impulse response model.

Insulin secretion rate (ISR) in vivo is reconstructed by deconvolution from plasma concentration of C-peptide (CP), a peptide with linear kinetics which is co-secreted with insulin but is not extracted by the liver. Deconvolution requires the knowledge of the CP impulse response. A two-exponential (2E) model is usually chosen to describe the CP impulse response but a one-exponential (1E) model is also used in the literature. The purpose here is to discuss the domain of validity of the 1E model in reconstructing the ISR by deconvolution. In particular, we show that the 1E model can be reliably used only if the ISR spectrum is concentrated in a narrow frequency band and a suitable input is designed for its identification.

Activity Cycles↗
PubMed1995

Insulin regulation of glucose turnover and lipid levels in obese children with fasting normoinsulinaemia.

To evaluate the early metabolic alterations induced by obesity, we studied glucose turnover and lipid levels in obese children with fasting normoinsulinaemia. Two experimental protocols were carried out. Protocol I consisted of a euglycaemic glucose clamp at two rates of insulin infusion. Protocol II was similar to protocol I except for a variable lipid infusion used to maintain basal non-esterified fatty acid (NEFA) levels. During protocol I, the glucose disappearance rates were lower in obese children, while no differences were found in hepatic glucose release. NEFA response to insulin was not substantially altered in obese children either at low or high insulin infusion. During protocol II, the NEFA clamp induced a 25% reduction in peripheral insulin sensitivity in control children whereas no changes were observed in obese children. Interestingly, lipid infusion in control children was not sufficient to reproduce the same degree of insulin resistance observed in obese children, suggesting that NEFA are only one of the determinants of insulin resistance at this stage of obesity. In conclusion, the present study provides a portrait of glucose metabolism and lipid levels in normoinsulinaemic obese children. Our results document that peripheral insulin resistance is the first alteration at this stage of obesity, whereas an increase in insulin secretion and a defect in the inhibition of hepatic glucose release by insulin may develop at a later stage. In addition, primarily receptor and post-receptor defects and some alterations of NEFA metabolism are likely to coexist in the induction of insulin resistance at this stage of obesity.

3-Hydroxybutyric Acid↗
PubMed1995

Compartmental modeling of glucagon kinetics in the conscious dog.

The aim of the present study was to examine glucagon metabolism and distribution using both compartmental-modeling approaches and steady-state organ-balance techniques in conscious, overnight-fasted dogs. Arterial plasma glucose concentrations were clamped at 14 mmol/L with a variable exogenous glucose infusion. Somatostatin was infused to block endogenous secretion of insulin and glucagon. Insulin was replaced intraportally at 2.4 pmol.kg-1.min-1 to maintain basal insulin concentrations in the range from 70 +/- 4 to 95 +/- 12 pmol/L. Glucagon was not given during the control period, but was subsequently infused peripherally in four 1-hour steps of 1.0, 3.0, 6.0, and 3.0 ng.kg-1.min-1. Glucagon levels increased from 0 to 68 +/- 6, 195 +/- 19, 378 +/- 47, and 181 +/- 20 ng/mL. Compartmental analysis of glucagon concentrations showed that glucagon was distributed in one compartment with a volume approximately equal to the plasma volume. The metabolic clearance rate of glucagon was 17.6 mL.kg-1.min-1. The liver cleared 24% of glucagon, and the kidneys, 17%.

Animals↗
PubMed1995

Bicarbonate kinetics in humans: identification and validation of a three-compartment model.

A model of bicarbonate kinetics is crucial to a correct interpretation of experiments for measuring oxidation in vivo of carbon-labeled compounds. The aim of this study is to develop a compartmental model of bicarbonate kinetics in humans from tracer data by devoting particular attention to model identification and validation. The data base consisted of impulse-dose studies of 14C-labeled bicarbonate in nine normal subjects. The decay curve of specific activity of CO2 in expired air (saRCO2) was frequently sampled for 4-7 h. In addition, endogenous production of CO2, VCO2, was measured by indirect calorimetry. A model of data, i.e., an exponential model, analysis of decay curves of saRCO2 showed first that three compartments are necessary and sufficient to describe bicarbonate tracer kinetics. Compartmental models were then used as models of system. To correctly describe the input-output configuration, labeled CO2 flux in the expired air, phi RCO2 (= saRCO2.VCO2), has been used as measurement variable in tracer model identification. A mammillary three-compartment model with a respiratory and a nonrespiratory loss has been studied. Whereas there is good evidence that respiratory loss takes place in the central compartment, whether nonrespiratory loss is taking place in the central compartment or in one of the two peripheral compartments is uncertain. Thus three competing tracer models were considered. Using a model-independent analysis of data, based on the body activity variable, to calculate mean residence time in the system, we have been able to validate a specific model structure, i.e., with the two irreversible losses taking place in the central compartment. This validated tracer model was then used to quantitate bicarbonate masses in the system. Because there is uncertainty about where endogenous production enters the system, lower and upper bounds of masses of bicarbonate in the body are derived.

Bicarbonates↗
PubMed1995

Glucose turnover in presence of changing glucose concentrations: error analysis for glucose disappearance.

The present studies were undertaken to determine whether 1) the cold- and hot-GINF techniques used with Steele's model provide equivalent estimates of the rates of glucose appearance (R(a)) and disappearance (R(d)) in the presence of physiological changes in glucose and insulin concentrations, 2) the conditions for the best estimation of R(a) are the same as those for R(d), 3) the magnitude of error (if present) differs in diabetic and nondiabetic subjects, and 4) situations exist in which the knowledge of R(d) allows inferences to be made on whole body glucose uptake. To do so we performed experiments in non-insulin-dependent diabetes mellitus and nondiabetic subjects using simultaneous infusions of [6-3H]glucose and [6-14C]glucose; glucose and insulin were infused to mimic normal postprandial glucose and insulin profiles; the infused glucose contained [6-14C]glucose but not [6-3H]glucose. Compared with the hot-GINF method, the traditional cold-GINF method underestimated (P < 0.05) R(a) and R(d) by 10-15% and hepatic glucose release by 25-50% during the 1st h of the study, with the magnitude of error being the same in both diabetic and nondiabetic subjects. Error analysis demonstrated that errors in R(a) and R(d) have different analytic expressions containing common structural but different volume errors. Both R(a) and R(d) can be accurately measured in diabetic and nondiabetic subjects if glucose specific activity is kept constant and the volume of the accessible pool is used to calculate glucose disappearance. The relationship between R(d) and whole body glucose uptake was also derived. Although R(d) can be determined by relying on measurements in the accessible pool only, the assessment of whole body glucose uptake requires a model of the nonaccessible portion of the glucose system. However, knowledge of R(d) can provide useful insights into the behavior of whole body glucose uptake.

Adult↗
PubMed1995

Kinetic analysis of thyroid hormone action on glucose metabolism in man.

Thyroid hormone action on insulin's effect on glucose kinetics was investigated with the use of a physiological three compartment model. In six healthy volunteers before and after 14 days of thyroxine treatment (300 micrograms/day), a bolus of [3-H3]glucose was injected and the time course of plasma radioactivity was followed closely for 150 min. Then a hyperinsulinemic (1 mU.min-1.kg-1) and euglycemic clamp was started, and euglycemia was maintained for another 250 min. A second bolus of the tracer was then given at 240 min, and the plasma radioactivity was followed for 160 min. Insulin stimulated basal plasma glucose clearance fourfold (p < 0.001) and completely suppressed basal hepatic glucose production (p < 0.001). Concomitantly, the total distribution volume of glucose was increased by 19% (p < 0.05); this change was accompanied by about 50% expansion of the slowly exchanging glucose pool (putatively representing the insulin-dependent compartment). Thyroxine treatment increased plasma triiodothyronine by about 20% (0.1 > p > 0.05) but did not affect basal glucose turnover, insulin-stimulated plasma glucose clearance or the insulin-induced suppression of endogenous glucose output. However, thyroxine treatment blunted the insulin-induced increases in total distribution volume and the slowly exchanging pool of glucose (p = NS vs the basal state). We conclude that minor changes in plasma triiodothyronine (such as occur during overfeeding) do not interfere with the ability of insulin to stimulate the rate of disappearance of glucose or suppress endogenous glucose release; however, our data suggest that they induce finer changes in glucose kinetics, possibly reflecting acceleration or intracellular glucose degradation.

Adult↗
PubMed1995

Estimation of beta-cell sensitivity from intravenous glucose tolerance test C-peptide data. Knowledge of the kinetics avoids errors in modeling the secretion.

Parametric models of insulin secretion are used to measure indexes of beta-cell function from plasma C-peptide concentration during an intravenous glucose tolerance test (IVGTT). Since the models have been usually assessed against plasma C-peptide data, both secretory and kinetic parameters need to be simultaneously estimated. However, undesired compensations between the two sets of parameters may arise. In this study, in order to evaluate IVGTT insulin secretion models, we have analyzed IVGTT data from seven normal subjects for whom individual C-peptide kinetics were known from a separate experiment. Three different beta-cell models have been examined: the minimal model M1 (Diabetes 37:223-231, 1988); a variation of a published model, M2 (Math Biosci 27:319-332, 1975); and a new one, M3. A two-compartment model was used to describe C-peptide kinetics. The results suggest the inadequacy of M1 since kinetic parameter estimates were consistently biased versus the known individual values, and systematic errors were present in the prediction of C-peptide data when kinetic parameters were fixed to the known individual values. M2 performs better than M1 since it reproduces C-peptide data satisfactorily when the individually known description of the kinetics is adopted. M3 retains the second-phase description of M2 but improves the description of first-phase release. M3 is thus proposed to reconstruct the insulin secretion time course and to estimate parameters of first- and second-phase sensitivity to glucose. We also show the robustness of M3, i.e., standard values of C-peptide kinetic parameters can be used when individual values are not available without a loss of accuracy in the estimated secretion parameters. Finally, the shortcomings of using a simplified single-compartment description of C-peptide kinetics are discussed.

Adult↗
PubMed1994

The effects of hormonal replacement therapy on insulin sensitivity in surgically postmenopausal cynomolgus monkeys (Macaca fascicularis).

OBJECTIVE: Our purpose was to evaluate the effect of hormone replacement therapy on insulin resistance in postmenopausal cynomolgus monkeys (Macaca fascicularis). STUDY DESIGN: We studied 37 surgically postmenopausal cynomolgus monkeys that were fed a moderately atherogenic diet for 12 weeks with either no treatment (control), conjugated equine estrogens, medroxyprogesterone acetate, combination conjugated equine estrogens and medroxyprogesterone acetate, or tamoxifen. Insulin sensitivity and glucose effectiveness were determined by the frequent-sampling intravenous tolerance test by means of the minimal model analysis. RESULTS: There were no differences in body weight, total plasma cholesterol, or body fat distribution between control and conjugated equine estrogens, medroxyprogesterone acetate, or combination treatment groups. However, compared with control animals (insulin sensitivity = 5.9 +2- 1.2 x 10(-4) min-1 microU-1 ml) or conjugated equine estrogens treatment (6.3 +/- 1.1 x 10(-4) min-1 microU-1 ml) insulin sensitivity was significantly decreased in animals treated with medroxyprogesterone acetate (2.9 +/- 0.4 x 10(-4) min-1 microU-1 ml, p < 0.001) or conjugated equine estrogens and medroxyprogesterone acetate (2.8 +/- 0.6 x 10(-4) min-1 microU-1 ml, p < 0.001). Although insulin sensitivity was shown to be decreased in the tamoxifen-treated animals (insulin sensitivity = 4.6 +/- 0.6 x 10(-4) min-1 microU -1 ml), the difference was not statistically significant compared with the control or conjugated equine estrogens-treated animals. No significant differences were seen for glucose effectiveness comparing control animals (glucose effectiveness = 0.043 +/- 0.006 min-1) to animals treated with medroxyprogesterone acetate (glucose effectiveness = 0.046 +/- 0.009 min-1), conjugated equine estrogens and medroxyprogesterone acetate (0.048 +/- 0.008 min-1) or tamoxifen (0.039 +/- 0.006 min-1). CONCLUSION: These results suggest that progestins alone or in combination with estrogens can induce insulin resistance in postmenopausal monkeys while having no effect on plasma lipid concentrations or glucose effectiveness.

Animals↗
PubMed1994

The dual tracer time-varying volume method for measuring hepatic glucose release in nonsteady state: theoretical and simulation results.

Measurement of hepatic glucose release in nonsteady state is difficult and experimental approaches have been developed in order to circumvent Steele's model inadequacy. Recently, a resurgence of interest in the time-varying volume method developed by Issekutz has taken place. Issekutz's approach assumes that the volume of Steele's model is not constant but time-varying and that its time course can be measured by infusing two tracers with different patterns. The time-varying volume is then substituted into Steele's equation and hepatic glucose release is estimated. The aim of this study was to analyze some basic aspects of Issekutz's method and to determine the accuracy of its estimate of hepatic glucose release. A theoretical analysis showed that the time-varying volume measured by Issekutz's approach is not unique but depends on the format of administration of the two tracers. In addition, such a volume allows an accurate estimate of hepatic glucose release if one of the two tracers is infused in such a way that its specific activity is maintained perfectly constant during the experiment. Since it is impossible to achieve a perfect clamp of specific activity, we also evaluated the performance of Issekutz's approach in more realistic experimental conditions which were reproduced by resorting to computer simulation. We simulated a euglycaemic clamp with insulin rising from basal to a plateau of approximately 40 microU/ml and then returning to basal. Nonsteady-state glucose kinetics were described by a previously validated two-compartment model while the time course of hepatic glucose release was derived from the literature. Both noise-free and noisy experimental conditions were simulated. We showed that the degree of accuracy of Issekutz's approach is very good and better than the one associated with the hot-ginf method. On the other hand, the major problem with Issekutz's approach is the sensitivity of the volume estimate to the measurement noise, which may limit its applicability in practice. In conclusion, we elucidated the theoretical grounds of Issekutz's approach and assessed its performance during nonsteady state in a realistic scenario using computer simulation.

Body Fluid Compartments↗
PubMed1994

Effect of naltrexone treatment on insulin secretion, insulin action and postprandial thermogenesis in obesity.

For many years a series of studies has been carried out to evaluate the role of endogenous opioid peptides on glucose metabolism. In this work we studied the influence of endogenous opioid peptides on insulin response to OGTT and glucose-induced thermogenesis before and after a prolonged oral treatment with Naltrexone (50 mg/daily for 6 days), an opioid receptor antagonist, in a group of 9 obese subjects. Moreover in obese patients we evaluated the effect of this anti-opioid drug on insulin secretion and insulin sensitivity during an IVGTT using the minimal model approach. We compared the pre-treatment results with data coming from a group of 5 normal-weight subjects. We measured blood glucose, plasma insulin and C-peptide concentrations and evaluated the following parameters: first (phi 1) and second (phi 2) phase of beta-cell sensitivity, insulin sensitivity and glucose effectiveness. Obese subjects displayed an increased insulin response to oral and i.v. glucose load, due to an increased first phase of insulin secretion (phi 1), a reduced insulin sensitivity (Si) and glucose effectiveness (Sg) in respect to normal-weight subjects. They showed no difference in glucose and insulin area during oral load and in their profiles during i.v. glucose load after naltrexone treatment. Similarly no significant variation in insulin sensitivity and glucose effectiveness was observed. The glucose-induced thermogenesis, measured by indirect calorimetry, was not modified by naltrexone. Therefore our study demonstrates that endogenous opioids do not play any role in the impairment of peripheral insulin sensitivity and energy expenditure in human obesity.

Adult↗
PubMed1994

Pulsatility does not alter the response to a physiological increment in glucagon in the conscious dog.

The present study was designed to investigate if pulsatile hyperglucagonemia of physiological magnitude has greater efficacy in stimulating hepatic glucose production than constant glucagon. Paired studies were performed in conscious dogs. After insulin and glucagon were clamped at basal concentrations for 2 h, glucagon was elevated for 4 h with either a continuous infusion or pulses having physiological frequency and amplitude. With continuous infusion, plasma glucagon concentrations increased from 56 +/- 7 to 194 +/- 27 ng/l. With pulsatile infusion, glucagon concentrations started at 53 +/- 6 ng/l and then oscillated between 157 +/- 15 and 253 +/- 28 ng/l. Plasma insulin concentrations remained constant at basal levels. Glucose production was determined using a time-varying two-compartment model for glucose kinetics and deconvolution. After 15 min, glucose production had risen from 13.6 +/- 1.1 to 53.8 +/- 3.9 mumol.kg-1.min-1 with continuous infusion and from 12.9 +/- 0.6 to 50.6 +/- 2.9 mumol.kg-1.min-1 with pulsatile infusion. After 4 h, the production had fallen to 16.1 +/- 1.2 and 17.1 +/- 0.7 mumol.kg-1.min-1. In the present animal model with insulin held constant, no difference was noted between the response to continuous or pulsatile glucagon infusion.

Animals↗
PubMed1994

Assessment of insulin action and glucose effectiveness in diabetic and nondiabetic humans.

Insulin concentrations in humans continuously change and typically increase only when glucose also increases such as with eating. In this setting, it is not known whether the severity of hepatic and extrahepatic insulin resistance is comparable and whether the ability of glucose to regulate its own uptake and release is defective in non-insulin-dependent diabetes mellitus (NIDDM). To address this question, NIDDM and nondiabetic subjects were studied when glucose concentrations were clamped at either 5 mM (euglycemia) or varied so as to mimic the glucose concentrations observed in nondiabetic humans after food ingestion (hyperglycemia). Insulin was infused so as to simulate a "nondiabetic" postprandial profile. During euglycemia, insulin increased glucose disposal in nondiabetic but not diabetic subjects indicating marked extrahepatic resistance. In contrast, insulin-induced suppression of glucose release was only minimally less (P < 0.05) in diabetic than nondiabetic subjects (-1.06 +/- 0.09 vs. -1.47 +/- 0.21 nmol.kg-1 per 4 h). Hyperglycemia substantially enhanced disposal in both groups. Glucose effectiveness measured as the magnitude of enhancement of disposal (0.59 +/- 0.18 vs. 0.62 +/- 0.17 nmollkg-1 per 4 h) and suppression of release (-0.36 +/- 0.12 vs. -0.14 +/- 0.12 nmol.kg-1 per 4 h) did not differ in the diabetic and nondiabetic subjects. In conclusion, when assessed in the presence of a physiological insulin profile, people with NIDDM demonstrate: (a) profound extrahepatic insulin resistance, (b) modest hepatic insulin resistance, and (c) normal ability of glucose to stimulate its own uptake and suppress its own release.

Blood Glucose↗
PubMed1994

Assessment of insulin action in NIDDM in the presence of dynamic changes in insulin and glucose concentration.

Both glucose and insulin are important regulators of glucose uptake and hepatic glucose release. Because insulin concentrations rarely if ever increase under daily living conditions, unless glucose concentrations also increase, we sought to determine whether hepatic and extrahepatic responses to changes in insulin and glucose concentration are impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). To address this question, glucose metabolism was measured in diabetic and nondiabetic subjects. A computer-driven infusion system was used to produce a nondiabetic postprandial insulin profile in both groups while sufficient exogenous glucose was infused to mimic nondiabetic postprandial glucose concentrations. Although NIDDM was associated with greater (P < 0.05) hepatic glucose release both before and during the prandial insulin infusion, suppression did not differ in the diabetic and nondiabetic subjects (-1.06 +/- 0.20 vs. -0.86 +/- 0.15 mmol/kg every 4 h). In contrast, stimulation of both glucose disappearance (0.77 +/- 0.27 vs. 1.68 +/- 0.27 mmol/kg every 4 h) and forearm glucose uptake (187 +/- 81 vs. 550 +/- 149 mumol/dl every 4 h) was lower (P < 0.05) in diabetic than in nondiabetic subjects. Thus, despite increased basal rates of glucose production, obese individuals with NIDDM had decreased stimulation of glucose disappearance but normal suppression of hepatic glucose release in response to nondiabetic prandial glucose and insulin concentrations. These data indicate that the increase in glucose that occurs with carbohydrate ingestion is likely to compensate for hepatic but not extrahepatic insulin resistance.

Blood Glucose↗
PubMed1994

Hyperinsulinemia decreases second-phase but not first-phase arginine-induced insulin release in humans.

The aim of this study was to investigate the effect of hyperinsulinemia on the first and second phase of arginine-induced insulin release in humans. Seven healthy subjects underwent three studies (lasting 360 min): a control study using saline infusion and two euglycemic clamps using a low-dose (0.33 mU.kg-1.min-1) and a high-dose (1.20 mU.kg-1.min-1) insulin infusion. After a 3-h equilibration period, arginine (25 g) was infused for 30 min, and insulin and C-peptide responses to arginine were followed for 180 min. At the end of the equilibration period, before arginine administration, steady-state insulin levels were (means +/- SE) 60.0 +/- 2.4, 165.6 +/- 1.8, and 455.4 +/- 7.8 pmol/l during saline, low-dose, and high-dose insulin infusions, respectively. The time course of insulin release during the arginine test was calculated from C-peptide concentrations by using C-peptide kinetic modeling and deconvolution. In particular, first-phase and second-phase insulin response was obtained by integrating the time course of the insulin release during either the first 5 min or the following 40 min of the arginine test, respectively. Whereas first-phase insulin release was independent of any effect induced by either insulin infusion, second-phase insulin release was reduced in a similar degree by both insulin infusion doses. First phase was 75.5 +/- 10.1, 73.7 +/- 12.8, and 73.4 +/- 10.3 pmol/kg, whereas second phase was 266.1 +/- 46.0, 143.1 +/- 33.5, and 133.0 +/- 30.2 pmol/kg for saline, low-dose, and high-dose insulin infusions, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

A minimal input-output configuration for a priori identifiability of a compartmental model of leucine metabolism.

To develop a model describing the structure and function of a metabolic system using data from an input-output experiment, it is useful to design a pilot tracer study first which contains a predicted maximal amount of information. Having postulated a physiologically reasonable model structure from the pilot data, two questions arise. First, are the model parameters a priori uniquely identifiable? That is, assuming an error-free model structure and data, can the parameters be uniquely identified from the information content of the pilot experiment? Second, if the model parameters are uniquely identifiable, is the pilot experiment a minimal one? That is, is the pilot experiment necessary and sufficient, in the sense of information content, among feasible experiments to guarantee a priori unique identifiability? The purpose of this paper is to determine a minimal input-output configuration for the a priori unique identifiability of a compartmental model describing the metabolism of leucine, an essential amino acid. The original pilot tracer experiment was a two-stage experiment consisting first of a two input-five output experiment followed by a single input-single output experiment. Here we show to guarantee a priori unique identifiability of the leucine model that the single input-single output experiment is not necessary, and that two of the outputs of the multi-input-multi-output experiment are not required.

Bicarbonates↗
PubMed1993

Estimation of protein fractional synthetic rate from tracer data.

The fractional synthetic rate (FSR) is a key parameter characterizing protein turnover that is estimated from tracer kinetic data. Formulas to estimate this parameter usually assume a precursor-product model. Assuming this model is correct, we discuss these formulas to estimate the FSR in the steady and non-steady state both for the radioactive and stable isotope tracer. Then we deal with the non-steady-state case where the FSR becomes time varying and derive formulas for its estimation. A non-steady-state case study on the flooding-dose technique for measuring protein turnover is presented.

Homeostasis↗