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Biomedical subjects

G Chauvet

Publications and source records attributed to G Chauvet.

At least 19 recordsLinked to original sources
PubMed2003

Fatty acid recycling in adipocytes: a role for glyceroneogenesis and phosphoenolpyruvate carboxykinase.

FA (fatty acid) recycling in adipose tissue appears to be an important pathway for regulating FA release into the blood during fasting. Re-esterification requires G3P (glycerol 3-phosphate), which cannot be synthesized from glucose because glycolysis is much reduced under such circumstances. In addition, G3P can scarcely originate from glycerol since glycerol kinase has a very low activity in white adipose tissue. It was shown about 35 years ago that a metabolic pathway named glyceroneogenesis, which allows G3P synthesis from non-carbohydrate precursors like pyruvate, lactate or amino acids, is activated during fasting. The major enzyme in this pathway was shown to be PEPCK-C [cytosolic phosphoenolpyruvate carboxykinase (GTP); EC 4.1.1.32]. The present review analyses the mechanisms by which a series of hormones and nutrients affect PEPCK-C gene transcription and glyceroneogenesis and describes evidence for dysregulation of this pathway in type 2 diabetes.

Adipocytes↗
PubMed2001

Identification of insulin domains important for binding to and degradation by endosomal acidic insulinase.

The endosomal compartment of hepatic parenchymal cells contains an acidic endopeptidase, endosomal acidic insulinase (EAI), which hydrolyzes internalized insulin at a limited number of sites. Although the positions of these cleavages are partially known, the residues of insulin important in its binding to and proteolysis by EAI have not been defined. To this end, we have studied the degradation over time of native human insulin and three insulin-analog peptides using a soluble endosomal extract from rat liver parenchyma followed by purification of the products by HPLC and determination of their structure by mass spectrometry. We found variable rates of ligand processing, i.e. high ([Asp(B10)]- and [Glu(A13),Glu(B10)]-insulin), moderate (insulin) and low (the H2-analog). On the basis of IC(50) values, competition studies revealed that human and mutant insulins display nearly equivalent affinity for the EAI. Proteolysis of human and mutant insulins by EAI resulted in eight cleavages in the B-chain which occurred in the central region (Glu(B13)-Leu(B17)) and at the C-terminus (Arg(B22)-Thr(B27)), the latter region comprising the initial cleavages at Phe(B24)-Phe(B25) (major pathway) and Phe(B25)-Tyr(B26) (minor pathway) bonds. Except for the [Glu(A13),Glu(B10)]-insulin mutant, only one cleavage on the A-chain was observed at residues Gln(A15)-Leu(A16). Analysis of the nine cleavage sites showed a preference for hydrophobic and aromatic amino acid residues on both the carboxyl and amino sides of a cleaved peptide bond. Using the B-chain alone as a substrate resulted in a 30-fold increase in affinity for EAI and a 6-fold increase in the rate of hydrolysis compared with native insulin. A similar role for the C-terminal region of the B-chain of insulin in the high-affinity recognition of EAI was supported by the use of the corresponding B(22)-B(30) peptide, which displayed an increase in EAI affinity similar to the entire B-chain vs. wild-type insulin. Thus, we have identified a highly specific molecular interaction of insulin with EAI at the aromatic locus Phe(B24)-Phe(B25)-Tyr(B26). Analytical subfractionation of a postmitochondrial supernatant fraction showed that a pulse of internalized [(125)I]Tyr(A14)-H2-analog, a protease-resistant insulin analog, undergoes a greater lysosomal transfer and lesser degradation than [(125)I]Tyr(A14)-insulin, confirming that endosomal sorting is regulated directly or indirectly by endosomal proteolysis.

Animals↗
PubMed2001

Processing of the insulin-like growth factor-II-mannose 6-phosphate receptor in isolated liver subcellular fractions.

A truncated, soluble form of the insulin-like growth factor-II-mannose 6-phosphate (IGF-II-M6P) receptor has been identified in serum and shown to be released from cultured tissues and cells, liver being the main contributor to serum receptor in adult rats. In the present study, the processing of the IGF-II-M6P receptor has been characterized in isolated liver subcellular fractions using ligand binding, affinity crosslinking, and Western immunoblotting techniques. The receptor in plasma membrane fractions differed from that in Golgi-endosomal fractions by: (i) a lower molecular size upon reducing polyacrylamide gel electrophoresis (245 vs. 255 kDa); (ii) a less tight membrane association as judged upon extractibility by NaCI; and (iii) the inability to recognize antibody anti-22C, directed against the cytoplasmic domain of the receptor. Incubation of cell fractions at 30 degrees C led to a pH- and time-dependent release of the receptor into the medium. The pH optimum for release was 5.5 in the Golgi-endosomal fraction and 7.5 in plasma membrane fractions; at this pH, approximately 2% and 20%-30% of total receptors were released per hour, respectively. Receptor release was inhibited in a dose-dependent manner by aprotinin, benzamidine, and leupeptin in the Golgi-endosomal fraction, and by 1,10 phenanthroline in plasma membrane fractions, although high concentrations were required for inhibition. The receptor released from Golgi-endosomes showed a 5-10 kDa reduction in size and a loss of ability to recognize antibody anti-22C, but that released from plasma membranes showed little or no changes in size. We conclude that soluble, carboxy-terminally truncated forms of the IGF-II-M6P receptor are generated from the intact receptor in isolated Golgi-endosomal and plasma membrane fractions. However, receptor processing in these fractions exhibits different properties, suggesting the involvement of different proteases.

Animals↗
PubMed2000

Insulin-induced redistribution of the insulin-like growth factor II/mannose 6-phosphate receptor in intact rat liver.

The ability of acute insulin treatment to elicit a redistribution of the liver insulin-like growth factor-II/ mannose 6-phosphate (IGF-II/M6P) receptor has been studied in rats, using cell fractionation. Injection of insulin (0.4-50 microg) led to a time- and dose-dependent decrease in IGF-II binding activity in Golgi-endosomal (GE) fractions, along with an increase in activity in the plasma membrane (PM) fraction; only receptor number was affected. Quantitative subfractionation of the microsomal fraction on sucrose density gradients showed that IGF-II binding activity distributed similarly to galactosyltransferase (a Golgi marker), at slightly higher densities than in vivo internalized (125)I-insulin, and at lower densities than 5' nucleotidase and alkaline phosphodiesterase (two plasma membrane markers). Insulin treatment led to a slight time-dependent and reversible shift of IGF-II binding activity toward higher densities. Subfractionation of the GE fraction on Percoll gradients showed that IGF-II binding activity was broadly distributed, with about 60% at low densities coinciding with galactosyltransferase and early internalized (125)I-insulin and with 40% at high densities in the region of late internalized (125)I-insulin. Insulin treatment caused a time-dependent and reversible shift of the distribution of IGF-II binding activity toward low densities. On SDS-PAGE, the size of the affinity-labeled IGF-II/M6P receptor was comparable in GE and PM fractions (about 255 kDa), but on Western blots receptor size was slightly lower in the latter (245 kDa) than in the former (255 kDa). Insulin treatment did not affect the size, but modified the abundance of the IGF-II/M6P receptor in a manner similar to that of IGF-II binding. In vivo chloroquine treatment fully suppressed the changes in IGF-II binding activity in liver GE and PM fractions observed in insulin-treated rats. We conclude that insulin elicits a time-dependent and reversible redistribution of liver IGF-II receptors from Golgi elements and endosomes to the plasma membrane, presumably via early endosomes.

Animals↗
PubMed1999

In vitro endosome-lysosome transfer of dephosphorylated EGF receptor and Shc in rat liver.

We have studied the endosome-lysosome transfer of internalized epidermal growth factor receptor (EGFR) complexes in a cell-free system from rat liver. Analytical subfractionation of a postmitochondrial supernatant fraction showed that a pulse of internalized [(125)I]EGF was largely associated with a light endosomal fraction devoid of lysosomal markers. After an additional 30 min incubation in vitro in the presence of an ATP-regenerating system, the amount of [(125)I]EGF in this compartment decreased by 39%, with an increase in [(125)I]EGF in lysosomes. No transfer of [(125)I]EGF to the cytosol was detected. To assess the fate of the internalized EGFR protein over the time course of the endo-lysosomal transfer of the ligand, the effect of a saturating dose of native EGF on subsequent lysosomal targeting of the EGFR was evaluated by immunoblotting. A massive translocation of the EGFR to the endosomal compartment was observed in response to ligand injection coincident with its tyrosine phosphorylation and receptor recruitment of the tyrosine-phosphorylated adaptor protein Shc. During cell-free endosome-lysosome fusion, a time-dependent increase in the content of the EGFR and the two 55- and 46-kDa Shc isoforms was observed in lysosomal fractions with a time course superimposable with the lysosomal transfer of the ligand; no transfer of the 66-kDa Shc isoform was detected. The relationship between EGFR tyrosine kinase activity and EGFR sorting in endosomes investigated by immunoblot studies with anti-phosphotyrosine antibodies revealed that endosomal dephosphorylation of EGFR and Shc preceded lysosomal transfer. These results support the view that a lysosomal targeting machinery distinct from the endosomal receptor kinase activity, such as the recruitment of the signaling molecule Shc, may regulate this sorting event in the endosome.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Endosome-lysosome transfer of insulin and glucagon in a liver cell-free system.

The endosome-lysosome transfer of in vivo internalized insulin and glucagon has been studied in a rat liver cell-free system and compared to that of galactosylated bovine serum albumin (GalBSA), a ligand of the asialoglycoprotein receptor. Density-gradient analysis of a postmitochondrial supernatant isolated 8 min after injection of [125I]iodoinsulin showed that the membrane-associated radioactivity (55% of the total) migrated as a single peak at the position of galactosyltransferase, a Golgi marker (1.08-1.10 g/ml). After incubation at 37 degrees C in the presence of ATP, an additional peak of radioactivity (12%) was detected at the position of acid phosphatase, a lysosomal marker (1.12-1.14 g/ml). No such peak was observed in a lysosome-depleted fraction. An ATP-dependent conversion of [125I]iodoinsulin to trichloroacetic-acid-soluble products occurred during incubation (20%) but this was unaffected by lysosome depletion. Gel-filtration and HPLC analysis of acid extracts of gradient fractions isolated after injection of [125I]iodoinsulins selectively labeled at tyrosine residues A14 or B26 revealed the presence of components which differed from intact iodoinsulins by size and/or hydrophobicity. Low molecular-mass components were less abundant and, conversely, intact iodoinsulin and/or high molecular-mass components more abundant in lysosomal fractions than in endosomal fractions. In vivo internalized [125I]iodoglucagon and [125I]iodogalBSA underwent a greater lysosomal transfer (17-21%) and lesser degradation (8-11%) than [125I]iodoinsulin. Glycyl-L-phenylalanine 2-naphtylamide and methionine O-methyl ester, two lysosome-disrupting enzyme substrates, partially released the radioactivity associated with lysosomal fractions (GalBSA > insulin = glucagon) but caused little or no release of that associated with endosomal fractions. Analysis of the alpha and beta subunits of the insulin receptor by cross-linking to [125I]iodoinsulin and Western immunoblotting, respectively, revealed a partial lysosomal transfer of these subunits during endosome-lysosome interaction. We conclude that an endosome-lysosome transfer of insulin and glucagon occurs in a liver cell-free system and suggest that the low recovery of these peptides in lysosomal fractions in vivo results from their rapid degradation within endosomes.

Animals↗
PubMed1998

Delay equation analysis of human respiratory stability.

A mathematical analysis of the stability in human respiration, based on the tau-decomposition method, is conducted on a simple, but realistic CO2 model of the respiratory system. This model incorporates a two-compartment representation (lungs and tissues) for the plant and a very general class of controller. By deriving an explicit stability criterion, the stability domain of the respiratory system can be characterized. We quantify the influence of four major parameters of respiratory instability, i.e. transport delay, lung volume, and equilibrium values of lung CO2 partial pressure and controller gain. We demonstrate the existence of a bifurcation point and periodic solutions, giving some characteristics of solutions near the bifurcation point.

Carbon Dioxide↗
PubMed1995

A mathematical analysis of intestinal peristaltic waves.

Gut motility is usually investigated by introducing probes in the intestinal lumen. Image analysis could be used instead of intraluminal pressure measurements to avoid the inconvenience of this invasive procedure. The present study exposes the theoretical principles of intestinal peristalsis in terms of indirect intraluminal pressure and content velocity measurements. A geometrical model of intestinal contractions is mathematically described by using Stokes' equations in order to evaluate velocities and pressures in the equations established by quantitative analysis of cinematography pictures. The couple velocity-pressure is calculated at each point of the geometrical model for a viscous and non-compressible fluid. This fluid flows in a geometrical structure, the boundaries of which vary with time and behave in a periodic and regular way by simulating the movements of intestinal contractions. A comparison is made between experimental pressure recordings in isolated rat intestines and pressure values calculated by utilizing the geometrical model. Velocity values calculated at every grid node show positive and negative zones in the geometrical model output. The position of these zones vary from one geometrical model to another. Moreover, the calculated pressure and velocity values change according to the applied vector efforts. The similarity of the results obtained shows the efficiency of the finite element technique in the case of Stokes' equations.

Animals↗
PubMed1993

An ACSL simulation of the respiratory system.

A simulation program for the respiratory system using ACSL (Advanced Continuous Simulation Language) is presented. The underlying model is based on the representation of ventilation as a phasic air movement in lungs during the respiratory cycle. The translation of the model with ACSL instructions is described in particular for continuous processes, such as respiratory gas exchanges, and discrete events, such as changes of respiratory phase. The advantages of using ACSL are discussed, and the utility of such a simulation program in both research and education is demonstrated.

Algorithms↗
PubMed1993

Mathematical study of periodic breathing as an instability of the respiratory system.

A theoretical study of respiratory stability, based on a simple CO2 model of the respiratory system, investigates each component of respiration: the plant system and the central and peripheral controller systems. Analysis of the dynamic properties of the plant leads to a simplified respiratory model for the study of the influence of the central and peripheral controller components on stability. It is shown that the central component is not involved in respiratory instability phenomena such as periodic breathing whereas the peripheral component plays a major role. The explicit analytical index of stability obtained allows definition of the conditions of occurrence of periodic breathing in terms of the fundamental respiratory parameters. Moreover, this index can be used to evaluate the influence of various respiratory parameters on the stability of respiration.

Carbon Dioxide↗
PubMed1993

Cyclic model of respiration applied to asymmetrical ventilation and periodic breathing.

A model taking into account the cyclic character of respiration in humans is developed using two classical simplifications: CO2 is the only respiratory gas involved; and respiration is regulated only by a CO2 linear controller. The model is used to investigate two important clinical aspects of respiratory disease: asymmetrical ventilation and periodic breathing. We show that asymmetry in ventilation significantly influences the time course of the CO2 partial pressure in the expired alveolar air at the mouth and the elimination of CO2 through the lungs. Furthermore, the CO2 controller delay plays a major role in periodic breathing.

Breath Tests↗
PubMed1991

A neural network model of the cerebellar cortex performing dynamic associations.

The present paper proposes a model which applies formal neural network modeling techniques to construct a theoretical representation of the cerebellar cortex and its performances in motor control. A schema that makes explicit use of propagation delays of neural signals, is introduced to describe the ability to store temporal sequences of patterns in the Golgi-granule cell system. A perceptron association is then performed on these sequences of patterns by the Purkinje cell layer. The model conforms with important biological constraints, such as the known excitatory or inhibitory nature of the various synapses. Also, as suggested by experimental evidence, the synaptic plasticity underlying the learning ability of the model, is confined to the parallel fiber--Purkinje cell synapses, and takes place under the control of the climbing fibers. The result is a neural network model, constructed according to the anatomy of the cerebellar cortex, and capable of learning and retrieval of temporal sequences of patterns. It provides a framework to represent and interpret properties of learning and control of movements by the cerebellum, and to assess the capacity of formal neural network techniques for modeling of real neural systems.

Animals↗
PubMed1990

Development of cytochrome b558 and oxidative metabolism in human granulocytes, monocytes and during differentiation of HL-60 and U 937 cells.

The development of cytochrome b558 (Cyt b) as determined spectrophotometrically, was investigated in human polymorphonuclear neutrophils (PMN), monocytes (MN) and during differentiation of HL-60 and U 937 cells induced by retinoic acid (RA) alone or in combination with IFN gamma. O2- release in response to a panel of stimulating agents, ie latex particles, opsonised zymosan, PMA, Con A and fMLP, was monitored by lucigenin-amplified chemiluminescence (CL). In parallel the expression of myeloperoxidase (MPO) was investigated and its catalytic activity on H2O2 related to luminol-amplified CL responses. In mature PMN and MN phagocytes, regardless of the stimulating agent, the O2- production is closely related to Cyt b but not to MPO specific contents. In differentiated HL-60 and U 937 cells, the oxidative metabolism increases in parallel with Cyt b specific contents, both being enhanced by the addition of IFN gamma to the RA treatment. However, marked differences in the O2- production intensities are observed depending on the stimulating agent tested and the state of differentiation considered. The PMA-stimulated O2- production is rather low ie 100 and 20 times less in granulocytic HL-60 and monocyto-macrophagic U 937 cells than in PMN and MN respectively. Latex, zymosan and Con A stimulated responses are close to those of MN, in monocyte-macrophagic U 937 cells. In conclusion, these data show that during differentiation; 1), Cyt b plays a critical role in O2- production; 2), the pathways leading to NADPH oxidase activation are diversely modulated following phagocyte differentiation with IFN gamma and/or with RA.

Acridines↗
PubMed1986

Habituation rules for a theory of the cerebellar cortex.

A quantitative model of cerebellar cortical function is described with a complete formalization based on (i) the topology of cerebellar cortical neuronal network, (ii) some particular synaptic properties of cell classes in cerebellum cortex, and (iii) the dynamics of excitation in this network. For (i), a construction of functional classes around one Purkinje cell is given and their existence is discussed. For (ii), as in Marr-Albus model, the modifiability of synapses between parallel fibres and Purkinje cell is assumed. But the formalization permits to consider the consequences of such a property at the level of glomerulus (with granule cells) which is known as a complex transformation system. For (iii) habituation rules are assumed. It is shown that this method leads to some interesting properties in the functioning of cerebellar cortex. Particularly, emitting frequency along a Purkinje cell axon results from a discrimination by the system between transformed input signals and an external "noise" due to all other "contexts," and learning could be considered as the result of a conflict between a set of patterns and the transformed input signals. This model could be a basis for future numerical simulations.

Animals↗
PubMed1986

An efficient structure for a medical information database in a general hospital.

This paper describes a Medical Information System (conversational in real-time). SIGMED, which is used in the French hospital of Angers. Its main feature is its original organization which (i) allows one to follow a patient's history in space and time with a limited number of medical items and the whole set of administration ones and makes it possible to carry and (ii) the possibility of various epidemiological studies relating to medical speciality records which contain all the medical information related to a patient's examination and/or hospitalization.

France↗
PubMed1986

[Estimate of the prevalence of rheumatoid arthritis based on a rheumatology study in the district of Angers].

The prevalence of rheumatoid arthritis is generally estimated to be 1 per cent, despite the marked differences between the various results published according to the survey techniques and the epidemiological criteria employed. The present survey consisted of patients from the target population (the 248,009 inhabitants of Angers over the age of 15 years), who had been examined by one of the hospital or private rheumatologists working in Angers between 1960 and 1984 and who were considered to be suffering from inflammatory rheumatism. The cases of rheumatoid arthritis included in this survey were still alive and were living in Angers between January 1 and June 30 1984 and corresponded to at least two of the New York criteria. The prevalence determined according to this technique was 0.17 per cent for two criteria and 0.11 per cent for three criteria. After discussing the bias and the particular conditions of the study, it appears that these particularly low levels are essentially related to: a recruitment bias due to the limitation of the survey to patients seen by rheumatologists, to the choice of New York criteria and more especially of 3 criteria which increases the specificity of the survey at the expense of the sensitivity, to the long observation (mean of 10.4 years) which contributed to a reduction in the number of false positives. The validity of this study is supported by the comparison with the study by O'Sullivan et al. also based 2 New York criteria with a follow-up of 3 to 5 years, which concluded on a prevalence of 0.24 per cent compared with 0.17 per cent in Angers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗