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B Canivet

Publications and source records attributed to B Canivet.

At least 55 records · Page 3Linked to original sources
PubMed1981

Glucagon degradation in isolated rat hepatocytes: effect of ammonium chloride and chloroquine.

It has recently been shown that, when [125I]glucagon is incubated with isolated rat hepatocytes at 37 degrees, the radiolabeled material is progressively internalized by the cell and is found to associate preferentially with lysosome-like structures. To assess the role of this process in the degradation of the hormone, the degradation of [125I]glucagon by isolated rat hepatocytes was examined both in incubation media and in cell extracts, after exposure of the radiolabelled hormone to hepatocytes in the absence and in the presence of lysosomotropic agents NH4Cl (8 mmoles/l) or chloroquine (10 micromoles/l); bacitracin (0.8 mg/ml, i.e. 0.6 mmoles/l) was present in all experimental conditions to minimize extracellular degradation. Neither NH4Cl nor chloroquine altered the time course and steady-state binding of [125I]glucagon, or the degradation of the hormone in incubation media. However, both agents partially inhibited the degradation of cell-associated [125I]glucagon in steady-state conditions. In dissociation experiments, NH4Cl, and even more so chloroquine, decreased the rate and the extent of release of radiolabelled material from the cells. Moreover, after 60 min dissociation, the presence of either agent resulted in less degradation of both cell-associated [125I]glucagon and that released into the medium. These results suggest that lysosomes are involved in the intracellular degradation of glucagon.

Ammonium Chloride↗
PubMed1981

The fate of [125I]iodoepidermal growth factor in isolated hepatocytes: a quantitative electron microscopic autoradiographic study.

When [125I]iodoepidermal growth factor is incubated with freshly isolated rat hepatocytes, cell-associated radioactivity reaches apparent steady state by 60 min at 20 C and by 30 min of incubation at 37 C. When the distribution of cell-associated radioactivity is studied at different times of incubation by quantitative electron microscopic autoradiography, the ligand initially associates with the plasma membrane and is progressively internalized as a function of time. The internalized ligand preferentially associates with lysosome-like structures. Qualitatively, these events are similar to those previously obtained with labeled insulin and glucagon in this cell, but quantitatively, the internalization of epidermal growth factor is much greater. The data suggest that the ligand or its specific receptor rather than the cell type is the major determinant of the rate of internalization.

Animals↗
PubMed1980

Glucocorticoid and catecholamine stimulation of amino acid transport in rat hepatocytes. Synthesis of a high-affinity component.

The kinetic properties of glucocorticoid and catecholamine stimulation of amino acid transport in freshly isolated rat hepatocytes were investigated. In the basal state (i.e., with hepatocytes incubated for 2 h in the absence of glucocorticoid or catecholamine), the saturable transport of alpha-aminoisobutyric acid (AIB) was accounted for mainly by a low-affinity component (Km for AIB approximately 5 mM). Hepatocyte exposure to cortisol (or dexamethasone), or to epinephrine for isoproterenol), for 2 h resulted in a 3- to 4-fold increase in the Vmax of a high-affinity component (Km for AIB approximately 1 mM) which was only weakly expressed in the basal state. Neither glucocorticoids nor catecholamines exerted a detectable effect on the low-affinity transport component. Cycloheximide prevented the emergence of the high-affinity component in hepatocytes exposed to dexamethasone or epinephrine. The results suggest that the stmulatory effect of glucocorticoids and catecholamines on amino acid transport in hepatocytes results from the synthesis of a high-affinity transport component.

Aminoisobutyric Acids↗
PubMed1980

C-peptide uptake and excretion by the liver in man.

The hepatic uptake of C-peptide is believed to be negligeable; this, however, is based on indirect evidence. In the present work, C-peptide was measured in four non obese non diabetic men stimultaneously in portal blood and bile. Small amounts of C-peptide were found in bile, compared with portal levels; these data are consistent with a minor role of the liver in C-peptide metabolism but represent a direct demonstration of an extraction of the peptide by the liver in man.

Adult↗
PubMed1980

Binding, internalization, and lysosomal association of 125I-glucagon in isolated rat hepatocytes. A quantitative electron microscope autoradiographic study.

When 125I-glucagon is incubated with freshly isolated rat hepatocytes and studied by quantitative electron microscope autoradiography, the labeled material localizes to the plasma membrane of the cell at early times of incubation of 20 degrees C; at later times of incubation at 20 degrees C, there is little further translocation of the labeled ligand. When incubations are carried out at 37 degrees C, the labeled material is progressively internalized by the cell after a brief delay. When the internalized radioactivity is further analyzed, it is found to associate preferentially with lysosome-like structures. When the cell-associated radioactivity is extracted, there is degradation of the ligand in incubations carried out at 37 degrees C. The events involved in the interaction of 125I-glucagon with the hepatocyte are similar to those previously described for labeled insulin in this cell. The process of binding, internalization, and lysosomal association appears to be a general process related to many polypeptide hormones and growth factors, and may represent the mechanism by which the specific binding of the ligand to the cell surface mediates the degradation of the ligand and the loss of its surface receptor.

Animals↗
PubMed1979

[Acute pancreatitis during "diabetic lipemia": unusual disclosure of insulin-dependent diabetes (author's transl)].

A case of diabetic lipemia is reported in a 27 year-old man admitted for acute pancreatitis. Initial investigations revealed gross hyperlipoproteinemia and ketoacidosis. Hyperlipoproteinemia was progressively corrected up to normalization in four weeks under insulin-therapy; the metabolic control of diabetes was obtained in parellel. This feature is caracteristic of "diabetic lipemia". The following sequence could be suggested: onset of diabetes, occurence of diabetic lipemia and then acute pancreatitis.

Acute Disease↗
PubMed1979

[Clinical value of the determination of carcinoembryonic antigen in bronchial secretion (author's transl)].

Determination of carcinoembryonic antigen (CEA) by radioimmunoassay was performed in per-endoscopic obtained bronchial secretion. Bronchial CEA values are higher in the case of primary carcinoma of the lung than of metastatic lung cancer or pulmonary benign disease (p less than 0.0005). More interesting is the ratio bronchial CEA/serum CEA which is much higher in primary carcinoma of the lung than in benign disease (p less than 0.0005) and lower in metastatic lung carcinoma than benign disease (p less than 0.0025). In primary carcinoma of the lung, the CEA determination seems to have a prognostic value since higher levels are reported in patients unsuccessfully treated than in treated patients with apparent remission.

Bronchi↗
PubMed1979

Somatostatin: lack of effect of cyclic AMP release and amino acid transport in isolated rat hepatocytes.

The aim of the present study was to determine whether or not somatostatin can directly affect amino acid transport and cyclic AMP (cAMP) release in isolated rat hepatocytes. Somatostatin at 1.5 microgram/ml (1mumol/l) had no effect on basal uptake of alpha-aminoisobutyric acid (AIB). Similarly, the peptide was without effect on basal cAMP release. Somatostatin exerted a slight but statistically not significant inhibitory effect on glucagon-stimulated AIB uptake and cAMP release. These observations do not support the possibility that somatostatin might directly interfere with hepatic glucose metabolism by altering the entry of amino acids into the liver and--or--by affecting the level of endogenous cAMP.

Aminoisobutyric Acids↗
PubMed1977

[Klinefelter's syndrome in 19 year old adolescents. (100 cases detected during selection for National Service)].

An analysis of 100 cases detected at the age of 19 years during selection for National Service. A somatic, genetic, psychological and hormonal profile emerges from this homogeneous sample. A study of olfactory function and insulin secretion was made. Testosterone deficiency was moderate, DHT deficiency being much more marked and insensitive to stimulation, suggestive of a 5 alpha-reductase defect. Impairment of oestrogenic function of the testis was demonstrated.

Adult↗
PubMedDate not supplied

Residual beta cell function in insulin-dependent diabetes: evaluation by circadian determination of C-peptide immunoreactivity.

Residual beta cell function was evaluated through circadian determination of C-peptide immunoreactivity (CPR) in eighty insulin-dependent diabetics. Evaluation of beta cell activity through circadian CPR determination was in good agreement with the results obtained by glucagon test which is considered a potent stimulus of C-peptide release. The prevalence of residual beta cell function in our population was 35%. Residual beta cell function was associated with a shorter duration of diabetes, a lower dose of insulin therapy and less chronic complications. On the other hand, serum growth hormone circadian variations were more spread in diabetics without beta cell function. That is consistent with diabetes instability which has been reported more commonly insulin-dependent diabetics without beta cell function.

Adolescent↗
PubMedDate not supplied

Inhibitory effects of metformin on insulin and glucagon action in rat hepatocytes involve post-receptor alterations.

The effect of the hypoglycaemic biguanide, metformin, on insulin binding and insulin action was investigated in rat hepatocyte monolayers. The binding of insulin was not modified in cultured cells exposed for 24 or 48 h to metformin at concentrations ranging from 1 mumol/l to 1 mmol/l, and no effect could be detected on insulin-induced down regulation. Metformin did not alter insulin stimulation of amino acid transport but the stimulatory effect of insulin on glycogen synthesis was reduced by 20%, 30% and 63% for metformin at 0.01, 0.1 and 1 mmol/l, respectively. Both responsiveness and sensitivity were altered by the biguanide. Metformin also inhibited basal glycogen synthesis and cellular glycogen contents were markedly decreased after exposure of cells to metformin (0.01-1 mmol/l). We also investigated the effect of metformin on glucagon action and metformin (0.1-1 mmol/l) was found to decrease the stimulatory effect of glucagon on amino acid uptake and on gluconeogenesis from alanine. These inhibitory effects of the biguanide were still observed when glucagon was replaced by dibutyryl cAMP. These in vitro studies demonstrate that: 1) metformin has no direct effect on insulin binding in hepatocytes, indicating that alteration of insulin stimulation of glycogen synthesis is due to modifications at the post receptor level. 2) metformin alters the action of glucagon in hepatocytes at a post AMP cyclase step. They also suggest that one of the mechanism of action of metformin may be to antagonize the effect of glucagon rather than to potentiate the action of insulin.

Amino Acids↗
PubMedDate not supplied

Receptor-linked degradation of 125I-insulin is mediated by internalization in isolated rat hepatocytes.

When hepatocytes were freshly isolated from rat liver and incubated for various periods of time at 37 degrees C, the media from the incubation, when completely separated from the cells, actively degraded 125I-insulin. THis soluble protease activity was strongly inhibited by bacitracin but was unaffected by the lysosomatropic agent ammonium chloride (NH4Cl). When hepatocytes were incubated with 125I-insulin at 37 degrees C in the presence or absence of 8 mM NH4Cl the ligand initially bound to the plasma membrane and was subsequently internalized as a function of time. When hepatocytes were incubated at 37 degrees C for 30 minutes with 125I-insulin in the presence of bacitracin and NH4Cl or bacitracin alone and the cells were washed, diluted, and the cell-bound radioactivity allowed to dissociate, the percent intact 125I-insulin in the cell pellet and in the incubation media was greater in the presence of NH4Cl at each time point of incubation. Under these same conditions a higher proportion of the cell-associated radioactivity was internalized and a higher proportion was associated with lysosomes. The data suggest that receptor-mediated internalization is required for insulin degradation by the cell, and that this process, at least in part, involves lysosomal enzymes. Furthermore, the data demonstrate that internalization is not blocked by the presence of bacitracin or NH4Cl in the incubation media, but that degradation is inhibited.

Ammonium Chloride↗
PubMedDate not supplied

Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.

OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (Néomercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basdène) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.

Adult↗