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Biomedical subjects

R Assan

Publications and source records attributed to R Assan.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pancreatic A cell response to arginine in the hibernating hedgehog (Erinaceus europaeus).

Pancreatic A cell response to arginine was measured in hedgehogs during the periods of lethargy and arousal and then during activity. Spontaneous plasma glucagon concentrations were lower during lethargy than during activity, and they increased during arousal. Arginine administration induced a slight, but significant delayed increase in plasma glucagon concentration in the lethargic hedgehog (body temperature: 6 degrees). During arousal, in vitro glucagon secretion was temperature dependent suggesting that body rewarming might, in itself, be an important stimulating factor of the A cells. In the presence of arginine, the glucagon output of the pancreas of lethargic hedgehogs was high at low temperatures. It decreased to a nadir at 19 degrees and increased up to 37 degrees. However, the basal or arginine-stimulated glucagon secretion of animals in lethargy was higher than that of animals in activity. These characteristics suggested the presence of a particular pool of cold-adapted enzymes in the A cells of lethargic hedgehogs.

Animals↗
PubMed1983

The nervous control of rat glucagon secretion in vivo.

In order to study the efferent pathways of the nervous regulation of rat A and B cells, portal blood samples were obtained in vivo without interruption of the blood flow. Glucagon, insulin and catecholamines were determined and hepatic blood flow (EHBF) was estimated by a Brome-Sulfone-Phtaleine extraction method. Carotid blood pressure was monitored and a normal volaemia was maintained. Stimulation of the right vagus nerve increased EHBF and the releases of glucagon and insulin. Stimulation of splanchnic nerve increased the glucagon and catecholamine secretions and decreased that of insulin. Acute hypovolaemia as induced by blood withdrawal, caused hormonal consequences similar to those of splanchnic stimulation. It is suggested that the nervous control of pancreatic islets plays an important role in the rat species. Assessment of the haemodynamic status is critical for the valid interpretation of pancreatic hormone concentrations in experimental conditions. A sympathetic stimulation can account for the high glucagon and relatively low insulin secretions which characterize the hormonal pattern of stress.

Animals↗
PubMed1983

Glucagon release after stimulation of the lateral hypothalamic area in rats: predominant beta-adrenergic transmission and involvement of endorphin pathways.

Catheterization of the portal vein and stereotaxic implantation of electrodes in the lateral hypothalamic area (LHA) were performed in normal rats after thiopental anesthesia. Immunoreactive glucagon (IRG) and insulin (IRI), glucose, catecholamines, and beta-endorphin were monitored in portal and peripheral plasma, before and during electrical stimulation of the LHA. The influences on glucose and hormone concentrations of propranolol, phentolamine, atropine, and naloxone infusions were also investigated in similar rats. A basal portoperipheral concentration gradient was found for IRG, IRI, and catecholamines, but not for beta-endorphin. The LHA stimulation induced a significant rise in portal catecholamine, IRG, and glucose concentrations; IRI remained unchanged; the portoperipheral catecholamine gradient was augmented. These alterations were not observed after bilateral splanchnicectomy. Propranolol infusion abolished the LHA-dependent IRG and glucose rises. Naloxone reduced the IRG rise significantly. Phentolamine and atropine did not modify the LHA-induced reactions. These results suggest that the glucagon release which follows LHA electrical stimulation depends mainly on beta-adrenergic transmission by the splanchnic nerves. Opioid peptide receptors may modulate this effect.

Animals↗
PubMed1983

Anti-islet immunity and thymic dysfunction in the mutant diabetic C57BL/KsJ db/db mouse.

Anti-islet immune reactions were studied in vitro in genetically diabetic homozygote C57BL/KsJ db/db mice, using murine islet cells as a target. Spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T-cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Anti-islet complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were also found in the sera of these mice. This anti-islet immunity was detectable as early as the tenth day of life and lasted throughout the entire life span of the animals. A significant lymphopenia was detected in thymus and spleen cell populations. None of these anomalies was found in control heterozygote mice. Thymic function was explored in the same mice by evaluating their serum thymic factor (FTS) levels using a rosette assay. The age-dependent decline of FTS levels was significantly accelerated in diabetic mice as compared with heterozygous littermates. Furthermore, FTS inhibitory immunoglobulins were detected in db/db mouse sera, which inactivated in vitro the biologic potency of synthetic FTS. Histologically, the thymus displayed an accelerated involution. It was shown by indirect immunofluorescence using anti-FTS monoclonal antibodies that the number of FTS+ cells was reduced in db/db mouse thymuses. Histologic study of the islets of Langerhans showed early signs of beta-cell hyperactivity and hypertrophy, followed by beta-cell rarefaction and profound dislocation of islet architecture. Insulitis was not detected.

Animals↗
PubMed1983

Reciprocal gastropancreatic modulations for the release of somatostatin-like immunoreactivity, glucagon, and insulin in the rat.

In order to assess the interrelationships between stomach and pancreas regarding the secretions of somatostatin-like immunoreactivity (SLI), glucagon (IRG), and insulin (IRI), concentrations of the three hormones were assayed in portal plasma and portal blood flow was measured in enterectomized rats before and after the selective removal of stomach or pancreas. Portal plasma SLI, IRG, and IRI concentrations were significantly increased by i.v. arginine in control rats (pancreas + stomach present). After gastrectomy, SLI, IRG, and IRI concentrations were, respectively, 52 +/- 13% (N = 15; P less than 0.005), 234 +/- 40% (P less than 0.001), and 119 +/- 15% (NS) of the pregastrectomy values. A decreased SLI secretion, an increased IRG release, and an unmodified basal IRI release were estimated by portal flow measurement. The A- and B-cell responses to arginine in the gastrectomized rats were significantly higher than in the control rats, while the D-cell response was no longer detectable. After pancreatectomy, by contrast, SLI concentrations were 360 +/- 75% of the prepancreatectomy values (N = 12; P less than 0.001). This reflected an actual increment of SLI release, taking into account the concomitant measurement of portal blood flow. The concentrations of IRG declined by 51 +/- 5% (P less than 0.001) and IRI was no longer measurable. A- and B-cell responses to arginine also were no longer detectable. These results suggest that in these experimental conditions (1) the stomach restrained pancreatic A- and B-cell responses to arginine, perhaps through the SLI released from the stomach and (2) the pancreas restrained gastric SLI secretion, perhaps through insulin.

Animals↗
PubMed1983

Anti-pancreatic immunity in genetically diabetic mice.

The anti-pancreatic immune reaction of genetically diabetic homozygote C57Bl/KsJ db/db mice was studied with an in vitro test using murine islet of Langerhans cells as target cells. C57Bl/KsJ db/db spleen lymphocytes inhibited insulin secretion by the islet cells. This inhibition was abolished when T cells were eliminated by treatment with anti-Thy 1.2 monoclonal antibody in the presence of complement. Together with this cell-mediated cytotoxicity, complement-dependent antibody (CDA) and antibody-dependent cell cytotoxicity (ADCC) were found in the sera of these mice. A longitudinal study showed that this anti-pancreatic toxicity was detectable as early as the 10th day of life and lasted throughout the entire life span of the animal. None of these anomalies was found in control heterozygote mice.

Aging↗
PubMed1983

[Mental function, functional hierarchy of the brain and glucoregulation].

Mental function in insulin-dependent diabetic (IDD) patients can be correlated with the endocrine and metabolic symptoms and signs of anxiety. In IDD patients, anxiety is usually accompanied by hyperactivity of the hyperglycemic hypothalamo-visceral axis. The hypothalamus is controlled by different superior nervous structures (limbic system and cortex) which, themselves, receive dopaminergic afferences. Two main patterns of reaction to anxiety associated with two distinct patterns of hypothalamo-visceral reactions, are suggested. In one, excessive hypothalamo-visceral reactions to stress can be associated with a deficient control of the hypothalamus. In the other, an appropriate control of the hypothalamus by limbic systems and prefrontal systems, via dopaminergic pathways, reduces the hyperglycemic reaction to stress. According to a psychosomatic approach, the principles of which are briefly recalled, some characterisation of mental function in IDD patients can be defined, as well as its psychiatric presentation. An improvement in mental function can be associated with a reduction in hypothalamic responses to the external or internal stimuli. An improvement in metabolic control can follow psychotherapy in such patients. Central dopaminergic pathways may play an important role in the control of anxiety and the subsequent endocrine and metabolic disorders caused by stress.

Blood Glucose↗
PubMed1982

[Inhibition of insulin secretion of mouse pancreatic cells by T lymphocytes of insulin-dependent diabetics].

We previously showed that circulating lymphocytes from more than 90% of insulin-dependent diabetics, block extra insulin secretion induced by stimulatory media in mouse pancreatic cells in vitro, without altering the secretion of glucagon. The present work demonstrates that this phenomenon depends on lymphocytes having the OKT3 marker, i.e., thymodependent lymphocytes. However, OKT4+ T helper cells are not required for the above phenomenon as proved by experiments using monoclonal sera against the OKT4 marker. When diabetes is associated with other autoimmune diseases, the pancreatic lymphocyte cytotoxicity observed in vitro is inhibited by the addition of a normal lymphocyte population; this could indicate that a "suppressor" factor is lacking in these patients. Conversely, addition of normal lymphocytes does not prevent lymphocyte cytotoxicity in diabetics without associated autoimmune diseases. Such a difference confirms the present trend to make a distinction between these two categories of diabetes.

Adolescent↗
PubMed1982

Absence of islet alpha cell function in pancreatectomized patients.

Plasma immunoreactive glucagon, C-peptide and substrates (glucose, lactate, and alanine) were measured in 21 pancreatectomized patients and 28 patients with chronic calcifying pancreatitis during arginine infusion. Results were compared with those obtained in control and in insulin-dependent diabetic subjects, and in pancreatectomized subjects receiving a combined infusion of glucagon and arginine or somatostatin and arginine. Plasma immunoreactive glucagon in the pancreatectomized patients was 230 +/- 26 pg/ml (control subjects 100 +/- 13 pg/ml, p less than 0.001), but was unchanged following arginine or somatostatin. Following ethanol extraction of plasma it became undetectable. Similar results were obtained in patients with chronic pancreatitis. In contrast to the insulin-dependent diabetic subjects, no changes in blood glucose, lactate, and alanine concentrations were found during arginine infusion in the pancreatectomized or pancreatitis patients. Addition of glucagon restored the metabolic response to arginine in the pancreatectomized patients. Our results confirm previous smaller studies that in pancreatectomized patients, A cell function is absent or insignificant.

Adult↗
PubMed1982

Virologic, immunologic, and genetic factors in insulin-dependent diabetes mellitus.

A 16-month-old girl presented with an episode of fever and acute thrombocytopenic purpura caused by a Coxsackie B5 virus. On days 13 to 23, laboratory evidence of diabetes mellitus was present, followed by a 2 1/2-month remission, then by definitive insulin-dependent diabetes. The involvement of virologic, immunologic, and genetic factors in the pathophysiology was substantiated by the following data: (1) Virus-induced glucose intolerance was produced in selected mouse strains. (2) Islet-cell antibodies were found one week before onset of diabetes; however, circulating lymphocytes of the child at that time suppressed insulin release from islets in vitro. (3) Immunogenetic analysis of the child revealed the presence of high-risk genetic markers. It is suggested that the convergence of an insulotropic variant virus, genetic predisposition, and perhaps some uncontrolled adjuvant factors, e.g. steroid therapy and DPT vaccination, may have determined insular damage and anti-islet autoimmune reactions, leading to insulin-dependent diabetes mellitus.

Antibodies↗
PubMed1982

The brain-islet axis: the nervous control of the endocrine pancreas.

The central nervous system exerts a control on the endocrine pancreas and can modulate the basic feed-back loop linking the concentration of the main energy substrates in blood with islet cell functions. Thus, the elementary glucose-insulin system can be modulated under physiological conditions by both the long-recognized entero-insular axis and by a brain-islet axis, particularly when insulin release occurs in anticipation of meals. Experimental stimulation or section of afferent nerves to the pancreas have demonstrated the existence of this nervous control. Changes in islet cell secretion during stress illustrate this influence under clinical conditions. A variety of experimental data suggest intervention of the brain-islet axis under the physiological circumstances: 1) Manipulation of certain hypothalamic centres followed by modification of feeding behaviour and of islet secretion. 2) Input to the brain is both humoral (carried by arterial carotid blood or the cerebrospinal fluid) and nervous, of sensory and visceral origins. Changes in these afferent pathways may influence islet secretion via the efferent pathways of the vagus and splanchnic nerves. 3) Besides acetylcholine and catecholamines, peptide neurotransmitters are likely to be involved in the transmission of these nervous inputs to islet cells. 4) Furthermore, hypothalamic factor (s) may also modify the endocrine pancreatic secretions.

Adrenergic Fibers↗
PubMed1982

The nervous control of rat somatostatin, glucagon and insulin secretions.

Somatostatin-like-immunoreactivity (SLI), immunoreactive insulin (IRI), glucagon (IRG) and catecholamine concentrations were measured in rat portal plasma during electrical stimulation of the vagus and splanchnic nerves, and during experimentally-induced hypovolaemia and hypoxaemia. Blood pressure, arterial gases and pH were monitored and hepatic blood flow was estimated (EHBF). Stimulation of the vagus nerves induced an increase in IRG and IRI concentrations, but had different influences on SLI level according to the concomitant experimental conditions. Stimulation of the left splanchnic nerve induced a sharp rise in SLI, IRG and catecholamine concentrations, whereas IRI level decreased hypovolaemia and hypoxaemia. Phentolamine treatment augmented the basal IRI, IRG and SLI concentrations. It did not suppress the hypovolaemia-induced rise of IRG and SLI concentrations, but unmasked a strong IRI release. By contrast, propranolol and atropine reduced significantly the A and D cell responses to acute hypovolaemia. These results are consistent with a profound influence of pancreatic nerves on A, B and D cell functions, which should be taken into account for interpretation of results during in vivo experiments.

Animals↗
PubMed1982

Diabetes mellitus following pentamidine-induced hypoglycemia in humans.

Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postabsorptive state. 28 +/- 1 microunits/ml (blood glucose 41 +/- 4 mg/dl) and 86 +/- 5 microunits/ml (blood glucose 15 +/- 5 mg/dl) vs. 15 +/- 3 microunits/ml in 10 control subjects and 55 +/- 3 microunits/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 microunits/ml vs. + 40 microunits/ml in control group and +77 microunits/ml in the insulinoma group), by i.v. arginine (maximal increment + 10 and +28 microunits/ml, respectively, vs. +55 in the controls and +90 microunits/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 microunits/ml, respectively) vs. +40 microunits/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10(-10) M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.

Adult↗