[Oral cimetidine does not induce hypersecretion of prolactin].
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Biomedical subjects
Publications and source records attributed to A Orsetti.
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The circulating lymphocyte because of its easy accessibility provides a useful model for the study of insulin receptors in dog. Consequently, we have studied the binding of insulin to lymphocytes prepared from Ficoll gradient. Our results demonstrate that circulating dog lymphocytes bind 125I-Insulin and this binding is inhibited by unlabeled insulin. This binding is function of the cell concentration and a saturable function of 125I-Insulin concentration. At 4 degrees C the equilibrium conditions are reached in 30 mn. Scatchard analysis revealed a cirvilinear plot. The number of receptors per cell was calculated as 1000 to 1500. This study have also revealated a decrease in the number of sites in diabetic dogs. We believe that the study of insulin receptor in lymphocyte's dog is important to understand some aspects of pathological states in diabetes.
Rejection of islet allografts is generally explained by immunologic problems, due to both cellular and antibody mechanisms. But another great problem is in the isolation of intact and viable islets of Langerhans: it is necessary to use a good method of pancreas distention, to determine the optimal concentration of collagenase for digestion, to select an effective technique for purifying the islets. This study correlates the morphology of isolated pancreatic islets of rats and dogs with secretion of insulin. The islets are incubated in a perifusion system and are tested during four periods; the glucose concentrations of the perifusion fluid are: 5.5 mM during the initial 70 min. period, 16.5 mM during the second 60 min. period, 5.5 mM during the third 60 min. period and 16.5 during the fourth 50 min. period. This "double glucose stimulation" is a good test of islet viability. The intact, viable isolated islets showed a significant increase of insulin secretion during the two 16.5 mM glucose periods. Damaged islets with some little morphologic alterations after showed a good insulin release during the first glucose stimulation, but a very poor insulin response to glucose during the second stimulation period.
Remission of juvenile insulin-dependent diabetes is a rare, temporary, and partial phenomenon which seems to be related to an improvement of the residual insulin secretion supported by prompt and rigorous insulin therapy. Thus, remissions allowing the replacement of insulin by oral drugs were attempted in 23 insulin dependent ketotic juvenile diabetics (age 10 +/- 2 years) of recent onset (apparent duration of diabetes 71 +/- 5 days) treated by an external artificial pancreas during 5 +/- 1 days and compared with 10 control diabetics treated by a less effective technique (preprogrammed insulin pump without feedback control) during 6 +/- 1 days. 18 (78%) remissions of long duration (1-26 months) occurred after artificial pancreas compared with 3 (30%) in the control group. Measurement of daily urinary C-peptide excretion confirmed the improvement of the residual insulin secretion in patients with insulin-induced remissions. Thus, the excellent blood glucose control given by an artificial pancreas seems necessary to lead to much more frequent remissions of diabetes than usually reported.
Nineteen patients suffering from chemical diabetes either with (group A, ten cases) or without (group B, nine cases) reactive hypoglycaemia were included in the study and compared with seven control (group C). The following variables were measured over a 5 hour period during a standard oral glucose tolerance test (OGTT): (i) blood glucose by continuous monitoring; (ii) plasma insulin and glucagon levels by radioimmunoassay. Furthermore, in five diabetics of group A, the data from the standard OGTT were compared with those from a pectin-supplemented OGTT (9 g per square meter of body surface). Although the insulin response was similar glucagon levels were significantly higher (45.1 +/- 11.8 pmol/l) (p less than 0.01) in group B than in group A (9.6 +/- 1.3) and C (8.1 +/- 1.4 at 30 minutes). The high glucagon levels noted in group B may explain the absence of reactive hypoglycaemia. The pectin supplementation improved the OGTT pattern by blunting the blood glucose peak (p less than 0.05), and avoiding the reactive hypoglycaemia (p less than 0.01). The addition of pectin did not produce any significant effect on the insulin response while a significant increase in glucagon concentrations (p less than 0.05) was observed beyond the 150th minute. Therefore, the data suggest that pectin may improve the OGTT pattern by increasing the glucagon response in the late period of the test. The development of postprandial reactive hypoglycaemia seldom coincides with a plasma glucagon peak, while the absence of reactive hypoglycaemia tends to be associated with high levels of glucagon, as is the case in overt diabetes mellitus.
Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.
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In the diabetic dog, the implantation of a bioartificial insulin distributor (Biard) producted a temporary normoglycemia, using islets of Langerhans isolated from dog pancreas and cultured on the outer surface of the hollow fibers (XM 50). In a diabetic dog receiving the Biard using porcine isolated islets, the hyperglycemia was partially corrected during two days. In a diabetic dog due to implantation of human isolated islets the slight rise of insulin and human C-peptide is not accompanied by significant decrease in hyperglycemia. However, in another diabetic dog the Biard implantation of human islets provoked a significant increase of insulin and human C-peptide in the blood, with partial normalisation of hyperglycemia during two days.
Islets of Langerhans were stablished in the spaces between 9 synthetic hollowfibers in a "bio-artificial insulin distributor" which was implanted in the carotid artery of totally pancreatectomized dogs. Normo-glycemia was restored after 4 hours. The major problem encountered was coagulation in the fibers. Presently, this limits the prolonged utilization of this system.
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In 14 patients anaesthetized before undergoing an orthopedic surgical intervention, the variations induced by anaesthesia in the 17 hydroxycorticosterone rate, catecholamine, somatotropic hormone (STH), insulin, glycemia, free fatty acids and thyrotropin (TSH), all these variations were studied before the surgery. The patients were divided into 2 groups of 7, the first one being anaesthestized by chlorprothixene dextromoramide Neurolept-Analgesia and the second one by Alfadione Fentanyl venous anaesthesia.
Experimental hyperthyroidism in the dog, and clinical hyperthyroidism in man, were studied as activation models of insulin catabolism. Plasma insulin and its A and B chains, were estimated by radioimmunoassay in 8 dogs, before and after daily administration of 1 mg of thyroxine per animal. A and B chains rose quite definitely under treatment, whereas the increase in blood insulin was only slight. Blood sugar did not vary. Glucose tolerance tests during treatment, showed that A and B chains did not follow a curve parallel to insulin were situated during the test, at a higher level in dogs treated with thyroxine than in controls. The estimations carried out in man, confirmed the high levels of the A and B chains in hyperthyroidism. The use of certain anti-insulin antisera for radioimmunoassay of insulin demonstrated cross reactions with A or B chains. This phenomenon may be the cause of excessive evaluation of plasma insulin in subjects with levels of circulating chains A and B. Chains A and B in the blood seem to be a sign of the level of metabolic destruction of the insulin and not that of secretion.
Continuous monitoring of a parameter is the more necessary the more fluctuant the studied parameter. Dosage upon discontinuously gained blood samples leads to a higher rate of interpretative errors. Our method of continuous investigation achieves a precise objectivation of the glycemia/insulinemia relationship; the automation assures a perfect comparability of the results.
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