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P Freychet

Publications and source records attributed to P Freychet.

At least 19 recordsLinked to original sources
PubMed1992

[Insulin receptors: structure and physiology].

Insulin receptor is a transmembrane glycoprotein. It is synthetized, in endoplasmic reticulum, as a proreceptor which is processed (glycosylation, proteolytic cleavage) and transported to the cell surface. The receptor is a hetero-tetramer comprising 4 subunits: the two alpha-subunits are extracellular; they are held, through disulfide bonds, to the beta-subunits. These are located across the membrane; their intracellular domain possesses a tyrosine-kinase activity. Insulin receptor gene has been located on chromosome 19 and its nucleotide sequence is known. The first functional property of the receptor is to recognize the hormone. Specific and high affinity binding site is supported by the alpha subunit. Shortly after insulin binding, the tyrosine-kinase is activated, resulting in autophosphorylation and phosphorylation of various substrates. Current research focuses on these nature of there substrates which activate intracellular putative mediators of insulin action. Insulin-resistant states are associated with functional alteration of the receptor. But only a few cases are directly related to nucleotide mutations at the level of the gene resulting in structurally abnormal receptor.

Receptor, Insulin↗
PubMed1992

Malignant pancreatic oncocytoma. An unusual cause of organic hypoglycemia.

A case of malignant islet-cell tumor with oncocytic features occurring in a 54-year-old woman with symptoms of organic hypoglycemia is reported. The tumor was composed of ribbons of cells arranged in an endocrine pattern. The cytoplasm of these cells was eosinophilic and finely granular. Ultrastructurally, the cells contained numerous mitochondria and dense-core neurosecretory granules. Tumor cells were focally immunoreactive for neuron-specific enolase, insulin, glucagon and VIP. Capillaries invasion and metastases to lymph nodes argued in favor of malignancy but there was no subsequent malignant involvement during a 3-year follow-up after surgery. Such insulinomas with oncocytic features have not been previously described. Endocrine features in oncocytomas of the pancreas and of other locations are discussed.

Adenoma↗
PubMed1992

Invasive mixed growth hormone/prolactin secreting pituitary tumour: complete shrinking by octreotide and bromocriptine, and lack of tumour growth relapse 20 months after octreotide withdrawal.

Octreotide and bromocriptine were used to treat an acromegalic patient harbouring an invasive pituitary tumour secreting growth hormone and prolactin. Octreotide (100 micrograms, subcutaneously, three times daily) and bromocriptine (15 mg orally, daily) rapidly improved clinical signs and symptoms, including diabetes that initially required insulin. Complete control of growth hormone and prolactin secretion was obtained and maintained by this treatment protocol for 12 months without affecting the other pituitary functions. A major tumour shrinkage was apparent by magnetic resonance imaging after six months, and was considered to be complete after 12 months of treatment. Octreotide was then discontinued without any relapse in either growth hormone secretion or tumour growth over a 20-month period following withdrawal. Attempts were made to discontinue bromocriptine, but a maintenance therapy (2.5 mg daily) was required to control rebounds of prolactin hypersecretion. Two months after octreotide withdrawal, acute pancreatitis secondary to cholelithiasis required surgery; this complication was attributed to octreotide (pre-treatment ultrasonography was normal). These findings suggest that combination therapy with octreotide and bromocriptine may be considered in pituitary macroadenomas secreting growth hormone and prolactin. They also emphasize the need for a close monitoring of cholelithiasis, not only during octreotide therapy but also after the drug's withdrawal.

Adenoma↗
PubMed1990

Autoantibodies to the insulin receptor are infrequent findings in type 1 (insulin-dependent) diabetes mellitus of recent onset.

To determine whether autoantibodies to the insulin receptor may represent markers of Type 1 (insulin-dependent) diabetes, the prevalence of such antibodies was investigated in sera of 60 newly diagnosed untreated Type 1 diabetic patients. A sensitive assay, based on enzyme linked immunosorbent assay has been set up which detects antibodies to the insulin receptor irrespective of their potentially inhibiting effect on insulin binding. Moreover, this method allows easy determination of the immunoglobulin class involved in the anti-receptor activity. Among the 60 sera examined, only one was found to contain anti-insulin receptor autoantibodies (IgG class). In view of our data, we conclude that autoantibodies to the insulin receptor are infrequent findings in Type 1 diabetes of recent onset.

Adolescent↗
PubMed1987

Insulin receptor kinase is hyperresponsive in adipocytes of young obese Zucker rats.

Thirty-day-old obese Zucker rats have hyperresponsive adipose tissue, whereas their skeletal muscle normally responds to insulin in vitro. To further substantiate the role of insulin receptor tyrosine kinase in insulin action, we have studied the kinase activity of receptors obtained from adipocytes and skeletal muscle of these young obese Zucker rats. Insulin receptors, partially purified by wheat germ agglutinin agarose chromatography from plasma membranes of isolated adipocytes or from skeletal muscles, were studied in a cell-free system for auto-phosphorylation and for their ability to phosphorylate a synthetic glutamate-tyrosine copolymer. For an identical amount of receptors, the insulin stimulatory action on its beta-subunit receptor phosphorylation was markedly augmented in preparations from hyperresponsive adipocytes of obese animals compared with lean rats. Basal phosphorylation of adipocyte insulin receptors was nearly identical in lean and obese animals. Similarly the capacity of adipocyte insulin receptors to catalyze the phosphorylation of the synthetic substrate in response to insulin was increased. By contrast, the kinase activity of insulin receptors prepared from normally insulin-responsive skeletal muscle was similar in preparations of lean and obese rats. These results show that a state of hyperresponsiveness to insulin is correlated with a parallel increase of insulin receptor kinase activity suggesting an important role for this activity in insulin action.

Adipose Tissue↗
PubMed1986

Internalization and recycling of 125I-photoreactive insulin-receptor complexes in hepatocytes in primary culture.

When the insulin receptor is tagged with a 125I-photoreactive insulin analogue that can be covalently coupled to it by UV irradiation, the fate of this labeled receptor can be followed both morphologically and biochemically. In the present study we have applied this tool to trace the pathway followed by 125I-photoreactive insulin-receptor complex in hepatocytes in primary culture. As determined by quantitative electron microscopic autoradiography, the internalized labeled material first associates with clear vesicles, second is found in multivesicular bodies, third associates with dense bodies and fourth returns to the cell surface via clear vesicles. This recycling process is inhibited by lysosomotropic agents, i.e. NH4Cl or chloroquine. These data confirm, in another cell system, our previous observations carried out in freshly isolated rat hepatocytes and demonstrate the feasibility and complementarity of both freshly isolated hepatocytes and hepatocytes in primary culture to study internalization and recycling of the insulin receptor.

Ammonium Chloride↗
PubMed1986

Intracellular pathway followed by the insulin receptor covalently coupled to 125I-photoreactive insulin during internalization and recycling.

After it interacts with a specific receptor on the cell surface, insulin is internalized in its target cell by an adsorptive endocytotic process and eventually degraded in lysosomes. It was also recently shown that the initial surface interaction between the hormone and its receptor is followed by an internalization of the receptor, which later is recycled back to the cell surface. In the present study the insulin receptor was tagged with a 125I-photoreactive insulin analogue that can be covalently coupled to the insulin receptor by ultraviolet irradiation. Using this tool we could trace by quantitative electron microscope autoradiography the intracellular pathway followed by this labeled receptor. The quantitative analysis of the intracellular distribution of the labeled material as a function of incubation time at 37 degrees C supports the following sequence of events: association first with clear vesicles, second with multivesicular bodies, third with dense bodies, and fourth, a return to the cell surface via clear vesicles. This insulin receptor recycling process is inhibited by monensin but unaffected by cycloheximide.

Animals↗
PubMed1986

Receptor-mediated endocytosis of polypeptide hormones is a regulated process: inhibition of [125I]iodoinsulin internalization in hypoinsulinemic diabetes of rat and man.

Much data suggest that receptor-mediated endocytosis is regulated in states of hormone excess. Thus, in hyperinsulinemic states there is an accelerated loss of cell surface insulin receptors. In the present experiments we addressed this question in hypoinsulinemic states, in which insulin binding to cell surface receptors is generally increased. In hepatocytes obtained from hypoinsulinemic streptozotocin-induced diabetic rats, [125I]iodoglucagon internalization was increased, while at the same time [125I]iodoinsulin internalization was decreased. The defect in [125I]iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of [125I]iodoinsulin was impaired; this defect was not present in insulin-treated patients. These data in the hypoinsulinemic rat and human diabetes suggest that receptor-mediated endocytosis is regulated in states of insulin deficiency as well as insulin excess. Delayed or reduced internalization of the insulin-receptor complex could amplify the muted signal caused by deficient hormone secretion.

Adolescent↗
PubMed1984

[C-peptide in the insulin-dependent diabetic].

Plasma C-peptide levels were measured in classical insulin-dependent diabetics (group I) and in patients who had become insulin-dependent after a mean 12 years of non-insulin dependent diabetes (group II). All had been under insulin therapy for no more than 2 years. Metabolic control, as assessed by blood glucose and glycosylated A1C haemoglobin levels, was equally poor in both groups. The doses of insulin required were almost identical, though slightly higher in group II, while C-peptide levels were twice as high in group II patients as in group I patients. These findings suggest that patients with initially non-insulin dependent diabetes are more resistant to insulin than classical insulin-dependent diabetics. This low sensitivity to insulin might be due to age (which was more advanced in our group II patients) or might indicate that these patients still retain a degree of insulin-resistance that is characteristic of non-insulin dependent diabetes.

Adult↗
PubMed1984

[Insulin resistance. Physiopathological and biochemical aspects].

New dimensions have been acquired in the physiopathology of insulin-resistant syndromes, by measurement of insulin receptors and advances in knowledge of their structure and function. The insulin-resistance of obese subjects and non-insulin dependent diabetics is related to both a reduction in the number of receptors, responsible for diminished sensitivity to insulin, and alterations in the action of the hormone at the post-receptor stage, with resulting suppression of the maximal response to insulin. The number of receptors varies as a function of blood insulin levels, hyperinsulinism being associated with a reduction in their number (negative feed-back). Post-receptor stages appear to be particularly sensitive to either absolute (insulin-dependent diabetes) or relative (non-insulin dependent diabetes) insulinopenia. The rare syndromes of extreme insulin resistance, often accompanied by acanthosis nigricans, represent a heterogeneous collection divisible into 3 sub-groups. In type A there is reduced insulin binding related to a possible primary anomaly (genetic) of the receptor. Type B is characterized by the presence of serum auto-antibodies directed against the receptor, while in type C the anomalies exist at the post-receptor stage. Insulin accelerates degradation of its specific receptor, a mechanism capable of explaining (at least partly) the negative feed-back control of the receptor by the hormone. The insulin-receptor complexes undergo intracellular transfer and a return to the plasmic membrane, but possible physiopathological implications of this movement have not been established. The receptor includes two principal glycoprotein subunits; alpha (130 kilodaltons) and beta (95 kilodaltons).(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗
PubMed1983

[Adsorption of insulin directly added to infusion bottles].

A study of insulin adsorption to infusion system was undertaken in the situation of direct addition of insulin alone in the infusion bottles, with use of 125I-labelled insulin and non labelled insulin. The infusion solutions tested were glucose solutions (5, 10, 15 and 30%). There is an important adsorption of insulin (75%) to the infusion system when the insulin concentration in the solution is low. The effluent insulin is not degraded. The glucose content of the solution does not influence the phenomenon. Adsorption of insulin decreases when the insulin concentration in the solution is increased and a plateau is reached starting from an insulin concentration in the solution of about 400 ng/ml; at higher concentrations, 80 to 90% of insulin that has been initially put in the bottle is recovered. Since the insulin concentrations in the solutions used in clinical practice are higher than 400 ng/ml, this adsorption phenomenon can be neglected and therefore can explain the efficiency of this mode of insulin-therapy. Kinetics of effluent insulin is a plateau, stable all along the infusion. Thus, direct addition of insulin alone into infusion bottles is an efficient and controlled mode of insulin-therapy if a minimal insulin concentration in the infused solution has been reached.

Adsorption↗
PubMed1983

[In vitro glucose consumption in severe hyperleukocytosis. A cause of factitious hypoglycemia].

Following the observation, in a patient with leukemia, of a factitious hypoglycemia that was related to in vitro glucose consumption by leukocytes, a study of glucose fall in vitro in the blood of 17 patients with leukemia of various types and with various grades of leukocytosis was undertaken. Results show that in vitro glucose consumption is linked to the intensity of leukocytes concentration, and is independant of the type of leukocyte. Factitious hypoglycemia may thus frequently occur in patients with high blood leukocyte count. This phenomenon, that was previously described, is again of interest to day because many laboratories do not yet use any more glycolysis inhibitors that partially inhibit it. Indeed, these inhibitors interfere with measures of other biological parameters that are simultaneously determined in autoanalysers.

Adult↗